chr13-95277072-C-T

Position:

• chr13-95277072-C-T

Variant summary

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

The NM_005845.5(ABCC4):​c.74+24169G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0918 in 152,074 control chromosomes in the GnomAD database, including 693 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 0.092 (693 hom., cov: 32)
• Consequence: ABCC4 NM_005845.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.389

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.135 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCC4	NM_005845.5	c.74+24169G>A		intron_variant		ENST00000645237.2	NP_005836.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCC4	ENST00000645237.2	c.74+24169G>A		intron_variant			NM_005845.5	ENSP00000494609	P1
	ENST00000701353.1	n.85-857C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0918 AC: 13950 AN: 151956 Hom.: 694 Cov.: 32

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.0624

Gnomad ASJ AF: 0.0997

Gnomad EAS AF: 0.0510

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.0500

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0824

Gnomad OTH AF: 0.0801

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

GnomAD4 genome AF: 0.0918 AC: 13958 AN: 152074 Hom.: 693 Cov.: 32 AF XY: 0.0895 AC XY: 6653 AN XY: 74348

Gnomad4 AFR AF: 0.126

Gnomad4 AMR AF: 0.0622

Gnomad4 ASJ AF: 0.0997

Gnomad4 EAS AF: 0.0507

Gnomad4 SAS AF: 0.144

Gnomad4 FIN AF: 0.0500

Gnomad4 NFE AF: 0.0825

Gnomad4 OTH AF: 0.0788

Alfa AF: 0.0830 Hom.: 555

Bravo AF: 0.0922

Asia WGS AF: 0.0850 AC: 297 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.90
DANN	Benign	0.76

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: rs4773866; hg19: chr13-95929326;