NM_004996.4:c.809+54C>A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 16 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 -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004996.4. 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
	ABCC1	NM_004996.4	MANE Select	c.809+54C>A		intron	N/A	NP_004987.2
	ABCC1	NM_019901.2		c.683+54C>A		intron	N/A	NP_063956.2
	ABCC1	NM_019902.2		c.809+54C>A		intron	N/A	NP_063957.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC1	ENST00000399410.8	TSL:1 MANE Select	c.809+54C>A		intron	N/A	ENSP00000382342.3
	ABCC1	ENST00000572882.3	TSL:1	c.809+54C>A		intron	N/A	ENSP00000461615.2
	ABCC1	ENST00000574224.2	TSL:1	n.884+54C>A		intron	N/A

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

African (AFR) AF: 0.761 AC: 25210 AN: 33134

American (AMR) AF: 0.143 AC: 6224 AN: 43550

Ashkenazi Jewish (ASJ) AF: 0.351 AC: 8690 AN: 24770

East Asian (EAS) AF: 0.0520 AC: 2047 AN: 39328

South Asian (SAS) AF: 0.173 AC: 14347 AN: 82812

European-Finnish (FIN) AF: 0.168 AC: 8845 AN: 52586

Middle Eastern (MID) AF: 0.309 AC: 1750 AN: 5668

European-Non Finnish (NFE) AF: 0.231 AC: 252117 AN: 1093624

Other (OTH) AF: 0.255 AC: 15179 AN: 59486

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

African (AFR) AF: 0.742 AC: 30690 AN: 41384

American (AMR) AF: 0.220 AC: 3370 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.347 AC: 1204 AN: 3466

East Asian (EAS) AF: 0.0439 AC: 228 AN: 5188

South Asian (SAS) AF: 0.169 AC: 816 AN: 4826

European-Finnish (FIN) AF: 0.157 AC: 1668 AN: 10592

Middle Eastern (MID) AF: 0.349 AC: 102 AN: 292

European-Non Finnish (NFE) AF: 0.234 AC: 15908 AN: 67972

Other (OTH) AF: 0.343 AC: 723 AN: 2110

Alfa AF: 0.279 Hom.: 23270

Bravo AF: 0.383

Asia WGS AF: 0.156 AC: 547 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.0060
DANN	Benign	0.44
PhyloP100		-0.69
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs903880; hg19: chr16-16130514; COSMIC: COSV60684840;