16-48224287-C-T

Variant names:

• chr16-48224287-C-T
• rs17822931
• NM_001370497.1:c.538G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 1P and 14B. PP3 BP4_Strong BP6_Moderate BA1

The NM_001370497.1(ABCC11):​c.538G>A​(p.Gly180Arg) variant causes a missense change. The variant allele was found at a frequency of 0.166 in 1,613,704 control chromosomes in the GnomAD database, including 38,952 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.14 (3460 hom., cov: 32)
  • Exomes 𝑓: 0.17 (35492 hom.)
• Consequence: ABCC11 NM_001370497.1 missense
• Clinical Significance: Benign criteria provided, single submitter B:4
• Conservation: PhyloP100: 4.13
• Publications: 142 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• PP3: Multiple lines of computational evidence support a deleterious effect 8: AlphaMissense, BayesDel_noAF, Cadd, Dann, MutationAssessor, PROVEAN, REVEL, REVEL [when BayesDel_addAF, max_spliceai, FATHMM_MKL, MetaRNN, MutationTaster, PrimateAI was below the threshold]
• BP4: Computational evidence support a benign effect (MetaRNN=1.0881486E-5).
• BP6: Variant 16-48224287-C-T is Benign according to our data. Variant chr16-48224287-C-T is described in ClinVar as Benign. ClinVar VariationId is 3558.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.818 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC11	NM_001370497.1	MANE Select	c.538G>A	p.Gly180Arg	missense	Exon 5 of 30	NP_001357426.1
	ABCC11	NM_001370496.1		c.538G>A	p.Gly180Arg	missense	Exon 5 of 30	NP_001357425.1
	ABCC11	NM_032583.4		c.538G>A	p.Gly180Arg	missense	Exon 6 of 31	NP_115972.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC11	ENST00000356608.7	TSL:1 MANE Select	c.538G>A	p.Gly180Arg	missense	Exon 5 of 30	ENSP00000349017.2
	ABCC11	ENST00000394747.5	TSL:1	c.538G>A	p.Gly180Arg	missense	Exon 4 of 29	ENSP00000378230.1
	ABCC11	ENST00000394748.5	TSL:1	c.538G>A	p.Gly180Arg	missense	Exon 5 of 30	ENSP00000378231.1

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21551 AN: 152078 Hom.: 3463 Cov.: 32

Gnomad AFR AF: 0.0286

Gnomad AMI AF: 0.310

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.838

Gnomad SAS AF: 0.427

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.126

GnomAD2 exomes AF: 0.224 AC: 56232 AN: 251088 AF XY: 0.232

Gnomad AFR exome AF: 0.0267

Gnomad AMR exome AF: 0.162

Gnomad ASJ exome AF: 0.108

Gnomad EAS exome AF: 0.870

Gnomad FIN exome AF: 0.235

Gnomad NFE exome AF: 0.129

Gnomad OTH exome AF: 0.169

GnomAD4 exome AF: 0.168 AC: 245580 AN: 1461508 Hom.: 35492 Cov.: 32 AF XY: 0.175 AC XY: 127485 AN XY: 727046

African (AFR) AF: 0.0218 AC: 731 AN: 33472

American (AMR) AF: 0.160 AC: 7157 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 2837 AN: 26122

East Asian (EAS) AF: 0.875 AC: 34730 AN: 39690

South Asian (SAS) AF: 0.404 AC: 34820 AN: 86174

European-Finnish (FIN) AF: 0.229 AC: 12224 AN: 53396

Middle Eastern (MID) AF: 0.0841 AC: 485 AN: 5768

European-Non Finnish (NFE) AF: 0.128 AC: 142076 AN: 1111810

Other (OTH) AF: 0.174 AC: 10520 AN: 60378

GnomAD4 genome AF: 0.142 AC: 21545 AN: 152196 Hom.: 3460 Cov.: 32 AF XY: 0.153 AC XY: 11395 AN XY: 74412

African (AFR) AF: 0.0285 AC: 1183 AN: 41536

American (AMR) AF: 0.113 AC: 1720 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.113 AC: 393 AN: 3472

East Asian (EAS) AF: 0.839 AC: 4340 AN: 5174

South Asian (SAS) AF: 0.426 AC: 2057 AN: 4826

European-Finnish (FIN) AF: 0.243 AC: 2575 AN: 10588

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.128 AC: 8708 AN: 67998

Other (OTH) AF: 0.125 AC: 264 AN: 2108

Alfa AF: 0.133 Hom.: 9382

Bravo AF: 0.130

TwinsUK AF: 0.123 AC: 456

ALSPAC AF: 0.131 AC: 506

ESP6500AA AF: 0.0314 AC: 138

ESP6500EA AF: 0.132 AC: 1136

ExAC AF: 0.225 AC: 27283

Asia WGS AF: 0.497 AC: 1723 AN: 3478

EpiCase AF: 0.120

EpiControl AF: 0.119

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, single submitter

Submissions by phenotype

APOCRINE GLAND SECRETION, VARIATION IN Benign:1

Feb 28, 2011

OMIM

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: literature only

not provided Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Colostrum secretion Benign:1

Feb 28, 2011

OMIM

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: literature only

Axillary odor Benign:1

Feb 28, 2011

OMIM

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: literature only

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.86
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Pathogenic	0.14
CADD	Pathogenic	29
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.34	T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.77	T
MetaRNN	Benign	0.000011	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Pathogenic	2.9	M
PhyloP100		4.1
PrimateAI	Benign	0.47	T
PROVEAN	Pathogenic	-6.5	D
REVEL	Pathogenic	0.70
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.58
MutPred		0.29		Loss of catalytic residue at V178 (P = 0.1257)
MPC		0.53
ClinPred		0.036	T
GERP RS		4.5
Varity_R		0.74
gMVP		0.54
Mutation Taster		=97/3	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs17822931; hg19: chr16-48258198; COSMIC: COSV62323034; COSMIC: COSV62323034;