Genetic Variant ABCB1:c.2927+377C>A (chr7-87518949-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001348946.2(ABCB1):c.2927+377C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0537 in 230,294 control chromosomes in the GnomAD database, including 647 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.064 ( 540 hom., cov: 32)

Exomes 𝑓: 0.034 ( 107 hom. )

Consequence

ABCB1
NM_001348946.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.291

Publications

5 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.138 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ABCB1	NM_001348946.2 link	c.2927+377C>A	intron_variant	Intron 23 of 27	ENST00000622132.5	NP_001335875.1
ABCB1	NM_001348945.2 link	c.3137+377C>A	intron_variant	Intron 27 of 31		NP_001335874.1
ABCB1	NM_000927.5 link	c.2927+377C>A	intron_variant	Intron 24 of 28		NP_000918.2	P08183-1A4D1D2
ABCB1	NM_001348944.2 link	c.2927+377C>A	intron_variant	Intron 25 of 29		NP_001335873.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCB1	ENST00000622132.5 link	c.2927+377C>A		intron_variant	Intron 23 of 27	1	NM_001348946.2	ENSP00000478255.1		P08183-1

Frequencies

GnomAD3 genomes

AF:

0.0635

AC:

9657

AN:

152108

Hom.:

537

Cov.:

show subpopulations

Gnomad AFR

AF:

0.141

Gnomad AMI

AF:

0.0680

Gnomad AMR

AF:

0.0462

Gnomad ASJ

AF:

0.0257

Gnomad EAS

AF:

0.141

Gnomad SAS

AF:

0.0506

Gnomad FIN

AF:

0.0311

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0223

Gnomad OTH

AF:

0.0559

GnomAD4 exome

AF:

0.0344

AC:

2684

AN:

78068

Hom.:

107

Cov.:

AF XY:

0.0337

AC XY:

1342

AN XY:

39872

show subpopulations

African (AFR)

AF:

0.119

AC:

304

AN:

2550

American (AMR)

AF:

0.0519

AC:

214

AN:

4126

Ashkenazi Jewish (ASJ)

AF:

0.0196

AC:

AN:

2192

East Asian (EAS)

AF:

0.137

AC:

613

AN:

4476

South Asian (SAS)

AF:

0.0385

AC:

291

AN:

7564

European-Finnish (FIN)

AF:

0.0305

AC:

108

AN:

3546

Middle Eastern (MID)

AF:

0.0278

AC:

AN:

324

European-Non Finnish (NFE)

AF:

0.0194

AC:

945

AN:

48770

Other (OTH)

AF:

0.0347

AC:

157

AN:

4520

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

126

252

377

503

629

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

128

160

<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:

0.0635

AC:

9673

AN:

152226

Hom.:

540

Cov.:

AF XY:

0.0637

AC XY:

4739

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.141

AC:

5871

AN:

41520

American (AMR)

AF:

0.0463

AC:

708

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.0257

AC:

AN:

3468

East Asian (EAS)

AF:

0.140

AC:

728

AN:

5190

South Asian (SAS)

AF:

0.0498

AC:

240

AN:

4820

European-Finnish (FIN)

AF:

0.0311

AC:

330

AN:

10600

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0223

AC:

1514

AN:

68020

Other (OTH)

AF:

0.0581

AC:

123

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

433

867

1300

1734

2167

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

192

288

384

480

<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:

0.0403

Hom.:

488

Bravo

AF:

0.0695

Asia WGS

AF:

0.0890

AC:

310

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

6.8

(source)

DANN

Benign

0.72

PhyloP100

0.29

Mutation Taster

=98/2

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

Computational scores

Splicing

Publications

Other links and lift over