rs2230669

Variant names:

• chr16-16044456-G-A
• rs2230669
• NM_004996.4:c.816G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-16044456-G-A
• chr16-16044456-G-T

Variant summary

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

The NM_004996.4(ABCC1):​c.816G>A​(p.Pro272Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0539 in 1,612,626 control chromosomes in the GnomAD database, including 2,668 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 0.049 (197 hom., cov: 32)
  • Exomes 𝑓: 0.054 (2471 hom.)
• Consequence: ABCC1 NM_004996.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.23
• Publications: 15 publications found

Genes affected

ABCC1 (HGNC:51): (ATP binding cassette subfamily C member 1 (ABCC1 blood group)) 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 full transporter is a member of the MRP subfamily which is involved in multi-drug resistance. This protein functions as a multispecific organic anion transporter, with oxidized glutatione, cysteinyl leukotrienes, and activated aflatoxin B1 as substrates. This protein also transports glucuronides and sulfate conjugates of steroid hormones and bile salts. Alternatively spliced variants of this gene have been described but their full-length nature is unknown. [provided by RefSeq, Apr 2012]

ABCC1 Gene-Disease associations (from GenCC):

• hearing loss, autosomal dominant 77

  Inheritance: AD, Unknown Classification: MODERATE, LIMITED Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae)
• autosomal dominant nonsyndromic hearing loss

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP7: Synonymous conserved (PhyloP=-2.23 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0593 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC1	NM_004996.4	c.816G>A	p.Pro272Pro	synonymous_variant	Exon 8 of 31	ENST00000399410.8	NP_004987.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC1	ENST00000399410.8	c.816G>A	p.Pro272Pro	synonymous_variant	Exon 8 of 31	1	NM_004996.4	ENSP00000382342.3

Frequencies

GnomAD3 genomes AF: 0.0490 AC: 7455 AN: 152190 Hom.: 197 Cov.: 32

Gnomad AFR AF: 0.0436

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.0409

Gnomad ASJ AF: 0.0504

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0136

Gnomad FIN AF: 0.0335

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.0609

Gnomad OTH AF: 0.0568

GnomAD2 exomes AF: 0.0427 AC: 10586 AN: 247784 AF XY: 0.0422

Gnomad AFR exome AF: 0.0439

Gnomad AMR exome AF: 0.0334

Gnomad ASJ exome AF: 0.0457

Gnomad EAS exome AF: 0.000111

Gnomad FIN exome AF: 0.0346

Gnomad NFE exome AF: 0.0603

Gnomad OTH exome AF: 0.0529

GnomAD4 exome AF: 0.0544 AC: 79458 AN: 1460318 Hom.: 2471 Cov.: 31 AF XY: 0.0536 AC XY: 38927 AN XY: 726536

African (AFR) AF: 0.0439 AC: 1468 AN: 33440

American (AMR) AF: 0.0339 AC: 1516 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.0478 AC: 1248 AN: 26126

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39692

South Asian (SAS) AF: 0.0167 AC: 1442 AN: 86234

European-Finnish (FIN) AF: 0.0359 AC: 1916 AN: 53406

Middle Eastern (MID) AF: 0.0901 AC: 511 AN: 5672

European-Non Finnish (NFE) AF: 0.0613 AC: 68075 AN: 1110698

Other (OTH) AF: 0.0544 AC: 3281 AN: 60336

GnomAD4 genome AF: 0.0490 AC: 7467 AN: 152308 Hom.: 197 Cov.: 32 AF XY: 0.0476 AC XY: 3542 AN XY: 74480

African (AFR) AF: 0.0437 AC: 1818 AN: 41560

American (AMR) AF: 0.0409 AC: 625 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0504 AC: 175 AN: 3472

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5182

South Asian (SAS) AF: 0.0143 AC: 69 AN: 4834

European-Finnish (FIN) AF: 0.0335 AC: 356 AN: 10618

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.0609 AC: 4142 AN: 68024

Other (OTH) AF: 0.0562 AC: 119 AN: 2116

Alfa AF: 0.0550 Hom.: 489

Bravo AF: 0.0496

Asia WGS AF: 0.0100 AC: 36 AN: 3478

EpiCase AF: 0.0616

EpiControl AF: 0.0622

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.79
DANN	Benign	0.48
PhyloP100		-2.2
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.6
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs2230669; hg19: chr16-16138313;