rs8047091

Variant names:

• chr16-48215007-T-C
• rs8047091
• NM_001370497.1:c.1122A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001370497.1(ABCC11):​c.1122A>G​(p.Lys374Lys) 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
• Publications: 12 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.

• 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.

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.1122A>G	p.Lys374Lys	synonymous	Exon 9 of 30	NP_001357426.1
	ABCC11	NM_001370496.1		c.1122A>G	p.Lys374Lys	synonymous	Exon 9 of 30	NP_001357425.1
	ABCC11	NM_032583.4		c.1122A>G	p.Lys374Lys	synonymous	Exon 10 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.1122A>G	p.Lys374Lys	synonymous	Exon 9 of 30	ENSP00000349017.2
	ABCC11	ENST00000394747.5	TSL:1	c.1122A>G	p.Lys374Lys	synonymous	Exon 8 of 29	ENSP00000378230.1
	ABCC11	ENST00000394748.5	TSL:1	c.1122A>G	p.Lys374Lys	synonymous	Exon 9 of 30	ENSP00000378231.1

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

GnomAD2 exomes AF: 0.150 AC: 37508 AN: 250708 AF XY: 0.148

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 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

African (AFR) AF: 0.338 AC: 11319 AN: 33454

American (AMR) AF: 0.110 AC: 4929 AN: 44652

Ashkenazi Jewish (ASJ) AF: 0.211 AC: 5512 AN: 26124

East Asian (EAS) AF: 0.0139 AC: 553 AN: 39692

South Asian (SAS) AF: 0.0886 AC: 7636 AN: 86230

European-Finnish (FIN) AF: 0.169 AC: 9019 AN: 53404

Middle Eastern (MID) AF: 0.235 AC: 1354 AN: 5768

European-Non Finnish (NFE) AF: 0.155 AC: 172257 AN: 1111488

Other (OTH) AF: 0.167 AC: 10074 AN: 60374

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

African (AFR) AF: 0.337 AC: 13950 AN: 41414

American (AMR) AF: 0.156 AC: 2379 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.200 AC: 696 AN: 3472

East Asian (EAS) AF: 0.0307 AC: 159 AN: 5184

South Asian (SAS) AF: 0.0748 AC: 360 AN: 4816

European-Finnish (FIN) AF: 0.167 AC: 1775 AN: 10598

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.162 AC: 11022 AN: 67962

Other (OTH) AF: 0.198 AC: 418 AN: 2112

Alfa AF: 0.175 Hom.: 10906

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.6
DANN	Benign	0.49
PhyloP100		-0.13
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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