chr13-95054859-T-C

Position:

• chr13-95054859-T-C

Variant summary

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

The NM_005845.5(ABCC4):​c.3367-1675A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.717 in 152,112 control chromosomes in the GnomAD database, including 40,694 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 0.72 (40694 hom., cov: 32)
• Consequence: ABCC4 NM_005845.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.22

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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.81 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCC4	NM_005845.5	c.3367-1675A>G		intron_variant		ENST00000645237.2	NP_005836.2
ABCC4	NM_001301829.2	c.3226-1675A>G		intron_variant			NP_001288758.1
ABCC4	XM_047430034.1	c.3238-1675A>G		intron_variant			XP_047285990.1
ABCC4	XM_047430035.1	c.2818-1675A>G		intron_variant			XP_047285991.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCC4	ENST00000645237.2	c.3367-1675A>G		intron_variant			NM_005845.5	ENSP00000494609.1
ABCC4	ENST00000646439.1	c.3226-1675A>G		intron_variant				ENSP00000494751.1
ABCC4	ENST00000643051.1	n.*1277+711A>G		intron_variant				ENSP00000495513.1
ABCC4	ENST00000643842.1	n.*3413-1675A>G		intron_variant				ENSP00000493861.1

Frequencies

GnomAD3 genomes AF: 0.717 AC: 108958 AN: 151994 Hom.: 40672 Cov.: 32

Gnomad AFR AF: 0.486

Gnomad AMI AF: 0.801

Gnomad AMR AF: 0.809

Gnomad ASJ AF: 0.783

Gnomad EAS AF: 0.740

Gnomad SAS AF: 0.818

Gnomad FIN AF: 0.758

Gnomad MID AF: 0.777

Gnomad NFE AF: 0.815

Gnomad OTH AF: 0.752

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.717 AC: 109020 AN: 152112 Hom.: 40694 Cov.: 32 AF XY: 0.718 AC XY: 53391 AN XY: 74366

Gnomad4 AFR AF: 0.486

Gnomad4 AMR AF: 0.809

Gnomad4 ASJ AF: 0.783

Gnomad4 EAS AF: 0.741

Gnomad4 SAS AF: 0.818

Gnomad4 FIN AF: 0.758

Gnomad4 NFE AF: 0.815

Gnomad4 OTH AF: 0.752

Alfa AF: 0.796 Hom.: 25643

Bravo AF: 0.709

Asia WGS AF: 0.767 AC: 2667 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.37
DANN	Benign	0.44

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: rs1189446; hg19: chr13-95707113;