NM_005845.5:c.3211-2793A>G

Variant names:

• chr13-95065652-T-C
• rs1678387
• NM_005845.5:c.3211-2793A>G

Variant summary

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

The NM_005845.5(ABCC4):​c.3211-2793A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.934 in 152,244 control chromosomes in the GnomAD database, including 66,540 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 0.93 (66540 hom., cov: 31)
• Consequence: ABCC4 NM_005845.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00600

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=-0.74).
• 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.3211-2793A>G		intron_variant	Intron 25 of 30	ENST00000645237.2	NP_005836.2
ABCC4	NM_001301829.2	c.3070-2793A>G		intron_variant	Intron 24 of 29		NP_001288758.1
ABCC4	XM_047430034.1	c.3082-2793A>G		intron_variant	Intron 25 of 30		XP_047285990.1
ABCC4	XM_047430035.1	c.2662-2793A>G		intron_variant	Intron 22 of 27		XP_047285991.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC4	ENST00000645237.2	c.3211-2793A>G		intron_variant	Intron 25 of 30		NM_005845.5	ENSP00000494609.1
ABCC4	ENST00000646439.1	c.3070-2793A>G		intron_variant	Intron 24 of 29			ENSP00000494751.1
ABCC4	ENST00000643051.1	n.*836-2793A>G		intron_variant	Intron 26 of 32			ENSP00000495513.1
ABCC4	ENST00000643842.1	n.*3257-2793A>G		intron_variant	Intron 26 of 31			ENSP00000493861.1

Frequencies

GnomAD3 genomes AF: 0.934 AC: 142121 AN: 152126 Hom.: 66488 Cov.: 31

Gnomad AFR AF: 0.916

Gnomad AMI AF: 0.940

Gnomad AMR AF: 0.940

Gnomad ASJ AF: 0.963

Gnomad EAS AF: 0.790

Gnomad SAS AF: 0.945

Gnomad FIN AF: 0.917

Gnomad MID AF: 0.949

Gnomad NFE AF: 0.955

Gnomad OTH AF: 0.946

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

GnomAD4 genome AF: 0.934 AC: 142230 AN: 152244 Hom.: 66540 Cov.: 31 AF XY: 0.932 AC XY: 69396 AN XY: 74444

Gnomad4 AFR AF: 0.916

Gnomad4 AMR AF: 0.940

Gnomad4 ASJ AF: 0.963

Gnomad4 EAS AF: 0.790

Gnomad4 SAS AF: 0.945

Gnomad4 FIN AF: 0.917

Gnomad4 NFE AF: 0.955

Gnomad4 OTH AF: 0.946

Alfa AF: 0.951 Hom.: 67683

Bravo AF: 0.935

Asia WGS AF: 0.868 AC: 3021 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	5.7
DANN	Benign	0.86

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: rs1678387; hg19: chr13-95717906;