chr16-48167600-G-A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001370497.1(ABCC11):c.3952C>T(p.Arg1318Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000366 in 1,612,318 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1318H) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000020 ( 0 hom. )

Consequence

ABCC11
NM_001370497.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.801

Publications

1 publications found

Variant links:

Genes affected

ABCC11 (HGNC:14639): (ATP binding cassette subfamily C member 11) The 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 ABC full transporter is a member of the MRP subfamily which is involved in multi-drug resistance. The product of this gene participates in physiological processes involving bile acids, conjugated steroids, and cyclic nucleotides. In addition, a SNP in this gene is responsible for determination of human earwax type. This gene and family member ABCC12 are determined to be derived by duplication and are both localized to chromosome 16q12.1. Multiple alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Jul 2008]

ABCC11 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.12326178).

BS2

High AC in GnomAd4 at 30 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001370497.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ABCC11	NM_001370497.1	MANE Select	c.3952C>T	p.Arg1318Cys	missense	Exon 29 of 30	NP_001357426.1	Q96J66-1
ABCC11	NM_001370496.1		c.3958C>T	p.Arg1320Cys	missense	Exon 29 of 30	NP_001357425.1
ABCC11	NM_032583.4		c.3952C>T	p.Arg1318Cys	missense	Exon 30 of 31	NP_115972.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ABCC11	ENST00000356608.7	TSL:1 MANE Select	c.3952C>T	p.Arg1318Cys	missense	Exon 29 of 30	ENSP00000349017.2	Q96J66-1
ABCC11	ENST00000394747.5	TSL:1	c.3952C>T	p.Arg1318Cys	missense	Exon 28 of 29	ENSP00000378230.1	Q96J66-1
ABCC11	ENST00000394748.5	TSL:1	c.3952C>T	p.Arg1318Cys	missense	Exon 29 of 30	ENSP00000378231.1	Q96J66-1

Frequencies

GnomAD3 genomes

AF:

0.000197

AC:

AN:

151910

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000700

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000664

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000359

AC:

AN:

250868

AF XY:

0.0000221

show subpopulations

Gnomad AFR exome

AF:

0.000492

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000199

AC:

AN:

1460408

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

726598

show subpopulations

African (AFR)

AF:

0.000777

AC:

AN:

33468

American (AMR)

AF:

0.00

AC:

AN:

43492

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000253

AC:

AN:

39554

South Asian (SAS)

AF:

0.00

AC:

AN:

86234

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111990

Other (OTH)

AF:

0.00

AC:

AN:

60352

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.000197

AC:

AN:

151910

Hom.:

Cov.:

AF XY:

0.000189

AC XY:

AN XY:

74196

show subpopulations

African (AFR)

AF:

0.000700

AC:

AN:

41428

American (AMR)

AF:

0.0000664

AC:

AN:

15060

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5152

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68030

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.547

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000190

Hom.:

Bravo

AF:

0.000230

ESP6500AA

AF:

0.000682

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000330

AC:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.37

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Uncertain

0.42

Eigen

Benign

-0.76

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.060

LIST_S2

Benign

0.85

M_CAP

Benign

0.027

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.43

MutationAssessor

Pathogenic

3.2

PhyloP100

0.80

PrimateAI

Benign

0.21

PROVEAN

Uncertain

-3.0

REVEL

Benign

0.21

Sift

Benign

0.047

Sift4G

Uncertain

0.059

Polyphen

0.0070

Vest4

0.20

MVP

0.72

MPC

0.12

ClinPred

0.12

GERP RS

2.2

Varity_R

0.091

gMVP

0.34

Mutation Taster

=96/4

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over