chr16-16036657-C-A

Variant names:

• chr16-16036657-C-A
• rs903880
• NM_004996.4:c.809+54C>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004996.4(ABCC1):​c.809+54C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 1,586,988 control chromosomes in the GnomAD database, including 59,895 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 0.36 (14389 hom., cov: 33)
  • Exomes 𝑓: 0.23 (45506 hom.)
• Consequence: ABCC1 NM_004996.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.688

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.735 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC1	NM_004996.4	c.809+54C>A		intron_variant	Intron 7 of 30	ENST00000399410.8	NP_004987.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC1	ENST00000399410.8	c.809+54C>A		intron_variant	Intron 7 of 30	1	NM_004996.4	ENSP00000382342.3

Frequencies

GnomAD3 genomes AF: 0.361 AC: 54903 AN: 151912 Hom.: 14347 Cov.: 33

Gnomad AFR AF: 0.741

Gnomad AMI AF: 0.312

Gnomad AMR AF: 0.221

Gnomad ASJ AF: 0.347

Gnomad EAS AF: 0.0438

Gnomad SAS AF: 0.170

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.344

Gnomad NFE AF: 0.234

Gnomad OTH AF: 0.347

GnomAD4 exome AF: 0.233 AC: 334409 AN: 1434958 Hom.: 45506 AF XY: 0.231 AC XY: 164450 AN XY: 713422

Gnomad4 AFR exome AF: 0.761

Gnomad4 AMR exome AF: 0.143

Gnomad4 ASJ exome AF: 0.351

Gnomad4 EAS exome AF: 0.0520

Gnomad4 SAS exome AF: 0.173

Gnomad4 FIN exome AF: 0.168

Gnomad4 NFE exome AF: 0.231

Gnomad4 OTH exome AF: 0.255

GnomAD4 genome AF: 0.362 AC: 54993 AN: 152030 Hom.: 14389 Cov.: 33 AF XY: 0.351 AC XY: 26109 AN XY: 74360

Gnomad4 AFR AF: 0.742

Gnomad4 AMR AF: 0.220

Gnomad4 ASJ AF: 0.347

Gnomad4 EAS AF: 0.0439

Gnomad4 SAS AF: 0.169

Gnomad4 FIN AF: 0.157

Gnomad4 NFE AF: 0.234

Gnomad4 OTH AF: 0.343

Alfa AF: 0.255 Hom.: 7663

Bravo AF: 0.383

Asia WGS AF: 0.156 AC: 547 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.0060
DANN	Benign	0.44
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs903880; hg19: chr16-16130514; COSMIC: COSV60684840;