chr13-95083350-G-T

Variant names:

• chr13-95083350-G-T
• rs1189437
• NM_005845.5:c.2536-60C>A

Variant summary

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

The NM_005845.5(ABCC4):​c.2536-60C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.943 in 1,587,350 control chromosomes in the GnomAD database, including 707,066 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 0.91 (62991 hom., cov: 29)
  • Exomes 𝑓: 0.95 (644075 hom.)
• Consequence: ABCC4 NM_005845.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.623

Genes affected

ABCC4 (HGNC:55): (ATP binding cassette subfamily C member 4 (PEL 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 protein is a member of the MRP subfamily which is involved in multi-drug resistance. This family member plays a role in cellular detoxification as a pump for its substrate, organic anions. It may also function in prostaglandin-mediated cAMP signaling in ciliogenesis. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Sep 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.949 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC4	NM_005845.5	c.2536-60C>A		intron_variant	Intron 20 of 30	ENST00000645237.2	NP_005836.2
ABCC4	NM_001301829.2	c.2395-60C>A		intron_variant	Intron 19 of 29		NP_001288758.1
ABCC4	XM_047430034.1	c.2407-60C>A		intron_variant	Intron 20 of 30		XP_047285990.1
ABCC4	XM_047430035.1	c.1987-60C>A		intron_variant	Intron 17 of 27		XP_047285991.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC4	ENST00000645237.2	c.2536-60C>A		intron_variant	Intron 20 of 30		NM_005845.5	ENSP00000494609.1

Frequencies

GnomAD3 genomes AF: 0.908 AC: 138025 AN: 152026 Hom.: 62949 Cov.: 29

Gnomad AFR AF: 0.828

Gnomad AMI AF: 0.940

Gnomad AMR AF: 0.926

Gnomad ASJ AF: 0.960

Gnomad EAS AF: 0.778

Gnomad SAS AF: 0.946

Gnomad FIN AF: 0.916

Gnomad MID AF: 0.934

Gnomad NFE AF: 0.955

Gnomad OTH AF: 0.930

GnomAD4 exome AF: 0.946 AC: 1358262 AN: 1435206 Hom.: 644075 AF XY: 0.947 AC XY: 675285 AN XY: 713072

Gnomad4 AFR exome AF: 0.823

Gnomad4 AMR exome AF: 0.926

Gnomad4 ASJ exome AF: 0.956

Gnomad4 EAS exome AF: 0.749

Gnomad4 SAS exome AF: 0.955

Gnomad4 FIN exome AF: 0.915

Gnomad4 NFE exome AF: 0.959

Gnomad4 OTH exome AF: 0.936

GnomAD4 genome AF: 0.908 AC: 138123 AN: 152144 Hom.: 62991 Cov.: 29 AF XY: 0.907 AC XY: 67464 AN XY: 74386

Gnomad4 AFR AF: 0.828

Gnomad4 AMR AF: 0.926

Gnomad4 ASJ AF: 0.960

Gnomad4 EAS AF: 0.778

Gnomad4 SAS AF: 0.946

Gnomad4 FIN AF: 0.916

Gnomad4 NFE AF: 0.955

Gnomad4 OTH AF: 0.929

Alfa AF: 0.948 Hom.: 85822

Bravo AF: 0.905

Asia WGS AF: 0.862 AC: 3000 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.5
DANN	Benign	0.26

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: rs1189437; hg19: chr13-95735604;