7-87550493-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001348946.2(ABCB1):c.1199G>A(p.Ser400Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0321 in 1,613,078 control chromosomes in the GnomAD database, including 1,007 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.026 ( 80 hom., cov: 33)

Exomes 𝑓: 0.033 ( 927 hom. )

Consequence

ABCB1
NM_001348946.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.0700

Publications

176 publications found

Variant links:

Genes affected

ABCB1 (HGNC:40): (ATP binding cassette subfamily B member 1) The membrane-associated protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the MDR/TAP subfamily. Members of the MDR/TAP subfamily are involved in multidrug resistance. The protein encoded by this gene is an ATP-dependent drug efflux pump for xenobiotic compounds with broad substrate specificity. It is responsible for decreased drug accumulation in multidrug-resistant cells and often mediates the development of resistance to anticancer drugs. This protein also functions as a transporter in the blood-brain barrier. Mutations in this gene are associated with colchicine resistance and Inflammatory bowel disease 13. Alternative splicing and the use of alternative promoters results in multiple transcript variants. [provided by RefSeq, Feb 2017]

ABCB1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008169949).

BP6

Variant 7-87550493-C-T is Benign according to our data. Variant chr7-87550493-C-T is described in ClinVar as Benign. ClinVar VariationId is 194008.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0256 (3906/152282) while in subpopulation NFE AF = 0.0402 (2734/68006). AF 95% confidence interval is 0.0389. There are 80 homozygotes in GnomAd4. There are 1815 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High AC in GnomAd4 at 3906 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
ABCB1	NM_001348946.2 link	c.1199G>A	p.Ser400Asn	missense_variant	Exon 11 of 28	ENST00000622132.5	NP_001335875.1
ABCB1	NM_001348945.2 link	c.1409G>A	p.Ser470Asn	missense_variant	Exon 15 of 32		NP_001335874.1
ABCB1	NM_000927.5 link	c.1199G>A	p.Ser400Asn	missense_variant	Exon 12 of 29		NP_000918.2
ABCB1	NM_001348944.2 link	c.1199G>A	p.Ser400Asn	missense_variant	Exon 13 of 30		NP_001335873.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
ABCB1	ENST00000622132.5 link	c.1199G>A	p.Ser400Asn	missense_variant	Exon 11 of 28	1	NM_001348946.2	ENSP00000478255.1
ABCB1	ENST00000265724.8 link	c.1199G>A	p.Ser400Asn	missense_variant	Exon 12 of 29	1		ENSP00000265724.3
ABCB1	ENST00000543898.5 link	c.1007G>A	p.Ser336Asn	missense_variant	Exon 11 of 28	5		ENSP00000444095.1

Frequencies

GnomAD3 genomes

AF:

0.0257

AC:

3906

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00717

Gnomad AMI

AF:

0.0537

Gnomad AMR

AF:

0.0279

Gnomad ASJ

AF:

0.0280

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0118

Gnomad FIN

AF:

0.0151

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0402

Gnomad OTH

AF:

0.0354

GnomAD2 exomes

AF:

0.0274

AC:

6863

AN:

250840

AF XY:

0.0285

show subpopulations

Gnomad AFR exome

AF:

0.00597

Gnomad AMR exome

AF:

0.0174

Gnomad ASJ exome

AF:

0.0272

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.0171

Gnomad NFE exome

AF:

0.0432

Gnomad OTH exome

AF:

0.0240

GnomAD4 exome

AF:

0.0328

AC:

47905

AN:

1460796

Hom.:

927

Cov.:

AF XY:

0.0325

AC XY:

23654

AN XY:

726744

show subpopulations

African (AFR)

AF:

0.00502

AC:

168

AN:

33478

American (AMR)

AF:

0.0182

AC:

815

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0271

AC:

707

AN:

26134

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39678

South Asian (SAS)

AF:

0.0147

AC:

1271

AN:

86254

European-Finnish (FIN)

AF:

0.0178

AC:

937

AN:

52634

Middle Eastern (MID)

AF:

0.0321

AC:

185

AN:

5760

European-Non Finnish (NFE)

AF:

0.0378

AC:

42070

AN:

1111756

Other (OTH)

AF:

0.0290

AC:

1749

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

2333

4666

6998

9331

11664

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1448

2896

4344

5792

7240

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0256

AC:

3906

AN:

152282

Hom.:

Cov.:

AF XY:

0.0244

AC XY:

1815

AN XY:

74474

show subpopulations

African (AFR)

AF:

0.00715

AC:

297

AN:

41552

American (AMR)

AF:

0.0279

AC:

426

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0280

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.0120

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.0151

AC:

160

AN:

10616

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0402

AC:

2734

AN:

68006

Other (OTH)

AF:

0.0350

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

198

397

595

794

992

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

160

200

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0347

Hom.:

413

Bravo

AF:

0.0260

TwinsUK

AF:

0.0345

AC:

128

ALSPAC

AF:

0.0353

AC:

136

ESP6500AA

AF:

0.00817

AC:

ESP6500EA

AF:

0.0385

AC:

331

ExAC

AF:

0.0290

AC:

3523

Asia WGS

AF:

0.00751

AC:

AN:

3478

EpiCase

AF:

0.0477

EpiControl

AF:

0.0476

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

May 22, 2014

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Oct 04, 2015

Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

ABCB1-related disorder

Benign:1

Jul 21, 2021

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Benign

0.96

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.12

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.52

T;.;T

MetaRNN

Benign

0.0082

T;T;T

MetaSVM

Benign

-0.39

MutationAssessor

Uncertain

2.1

M;M;.

PhyloP100

0.070

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.96

.;N;N

REVEL

Benign

0.26

Sift

Benign

0.36

.;T;T

Sift4G

Benign

0.33

T;T;T

Polyphen

0.0040

B;B;.

Vest4

0.024

MPC

0.20

ClinPred

0.0092

GERP RS

3.0

Varity_R

0.15

gMVP

0.45

Mutation Taster

=91/9

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over