rs8047091

chr16-48215007-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001370497.1(ABCC11):c.1122A>G(p.Lys374=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 1,613,234 control chromosomes in the GnomAD database, including 22,434 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 0.20 (3768 hom., cov: 32)
  • Exomes 𝑓: 0.15 (18666 hom.)
• Consequence: ABCC11 NM_001370497.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.127

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

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP7: Synonymous conserved (PhyloP=-0.127 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.332 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCC11	NM_001370497.1	c.1122A>G	p.Lys374=	synonymous_variant	9/30	ENST00000356608.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCC11	ENST00000356608.7	c.1122A>G	p.Lys374=	synonymous_variant	9/30	1	NM_001370497.1	P1

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30911 AN: 151930 Hom.: 3748 Cov.: 32

Gnomad AFR AF: 0.336

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.200

Gnomad EAS AF: 0.0306

Gnomad SAS AF: 0.0759

Gnomad FIN AF: 0.167

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.199

GnomAD3 exomes AF: 0.150 AC: 37508 AN: 250708 Hom.: 3422 AF XY: 0.148 AC XY: 20075 AN XY: 135526

Gnomad AFR exome AF: 0.335

Gnomad AMR exome AF: 0.106

Gnomad ASJ exome AF: 0.209

Gnomad EAS exome AF: 0.0295

Gnomad SAS exome AF: 0.0863

Gnomad FIN exome AF: 0.167

Gnomad NFE exome AF: 0.163

Gnomad OTH exome AF: 0.167

GnomAD4 exome AF: 0.152 AC: 222653 AN: 1461186 Hom.: 18666 Cov.: 33 AF XY: 0.151 AC XY: 109952 AN XY: 726908

Gnomad4 AFR exome AF: 0.338

Gnomad4 AMR exome AF: 0.110

Gnomad4 ASJ exome AF: 0.211

Gnomad4 EAS exome AF: 0.0139

Gnomad4 SAS exome AF: 0.0886

Gnomad4 FIN exome AF: 0.169

Gnomad4 NFE exome AF: 0.155

Gnomad4 OTH exome AF: 0.167

GnomAD4 genome AF: 0.204 AC: 30967 AN: 152048 Hom.: 3768 Cov.: 32 AF XY: 0.201 AC XY: 14952 AN XY: 74300

Gnomad4 AFR AF: 0.337

Gnomad4 AMR AF: 0.156

Gnomad4 ASJ AF: 0.200

Gnomad4 EAS AF: 0.0307

Gnomad4 SAS AF: 0.0748

Gnomad4 FIN AF: 0.167

Gnomad4 NFE AF: 0.162

Gnomad4 OTH AF: 0.198

Alfa AF: 0.172 Hom.: 5498

Bravo AF: 0.208

Asia WGS AF: 0.0840 AC: 293 AN: 3478

EpiCase AF: 0.172

EpiControl AF: 0.172

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	1.6
Dann	Benign	0.49

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

LitVar

Other links and lift over

dbSNP: rs8047091; hg19: chr16-48248918; COSMIC: COSV62326234; COSMIC: COSV62326234;