chr16-48170920-T-G

Variant names:

• chr16-48170920-T-G
• rs775703492
• NM_001370497.1:c.3746A>C

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001370497.1(ABCC11):​c.3746A>C​(p.Asp1249Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000212 in 1,461,756 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000021 (0 hom.)
• Consequence: ABCC11 NM_001370497.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.757
• Publications: 0 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.19921222).
• BS2: High AC in GnomAdExome4 at 31 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC11	NM_001370497.1	MANE Select	c.3746A>C	p.Asp1249Ala	missense	Exon 27 of 30	NP_001357426.1	Q96J66-1
	ABCC11	NM_001370496.1		c.3752A>C	p.Asp1251Ala	missense	Exon 27 of 30	NP_001357425.1
	ABCC11	NM_032583.4		c.3746A>C	p.Asp1249Ala	missense	Exon 28 of 31	NP_115972.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC11	ENST00000356608.7	TSL:1 MANE Select	c.3746A>C	p.Asp1249Ala	missense	Exon 27 of 30	ENSP00000349017.2	Q96J66-1
	ABCC11	ENST00000394747.5	TSL:1	c.3746A>C	p.Asp1249Ala	missense	Exon 26 of 29	ENSP00000378230.1	Q96J66-1
	ABCC11	ENST00000394748.5	TSL:1	c.3746A>C	p.Asp1249Ala	missense	Exon 27 of 30	ENSP00000378231.1	Q96J66-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000796 AC: 2 AN: 251134 AF XY: 0.00000737

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000212 AC: 31 AN: 1461756 Hom.: 0 Cov.: 30 AF XY: 0.0000234 AC XY: 17 AN XY: 727192

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.0000279 AC: 31 AN: 1111894

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000847 Hom.: 0

Bravo AF: 0.0000227

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.029	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	8.8
DANN	Benign	0.97
DEOGEN2	Uncertain	0.44	T
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.45	T
MutationAssessor	Benign	0.29	N
PhyloP100		0.76
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.20
Sift	Benign	0.27	T
Sift4G	Benign	0.39	T
Polyphen		0.010	B
Vest4		0.22
MutPred		0.48		Gain of MoRF binding (P = 0.1412)
MVP		0.75
MPC		0.12
ClinPred		0.054	T
GERP RS		2.4
Varity_R		0.17
gMVP		0.62
Mutation Taster		=84/16	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs775703492; hg19: chr16-48204831;