rs4148535

Variant names:

• chr13-95067540-G-A
• rs4148535
• NM_005845.5:c.3210+4122C>T

Your query was ambiguous. Multiple possible variants found:

• chr13-95067540-G-A
• chr13-95067540-G-C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM2 BP4_Strong BS1

The NM_005845.5(ABCC4):​c.3210+4122C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00103 in 151,898 control chromosomes in the GnomAD database, including 1 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 0.0010 (1 hom., cov: 31)
• Consequence: ABCC4 NM_005845.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.316

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 Likely_benign. Variant got -6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00103 (157/151898) while in subpopulation EAS AF= 0.0224 (115/5136). AF 95% confidence interval is 0.0191. There are 1 homozygotes in gnomad4. There are 98 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC4	NM_005845.5	c.3210+4122C>T		intron_variant	Intron 25 of 30	ENST00000645237.2	NP_005836.2
ABCC4	NM_001301829.2	c.3069+4122C>T		intron_variant	Intron 24 of 29		NP_001288758.1
ABCC4	XM_047430034.1	c.3081+4122C>T		intron_variant	Intron 25 of 30		XP_047285990.1
ABCC4	XM_047430035.1	c.2661+4122C>T		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.3210+4122C>T		intron_variant	Intron 25 of 30		NM_005845.5	ENSP00000494609.1
ABCC4	ENST00000646439.1	c.3069+4122C>T		intron_variant	Intron 24 of 29			ENSP00000494751.1
ABCC4	ENST00000643051.1	n.*835+4122C>T		intron_variant	Intron 26 of 32			ENSP00000495513.1
ABCC4	ENST00000643842.1	n.*3256+4122C>T		intron_variant	Intron 26 of 31			ENSP00000493861.1

Frequencies

GnomAD3 genomes AF: 0.00102 AC: 155 AN: 151780 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.000266

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000197

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0220

Gnomad SAS AF: 0.00436

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00192

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

GnomAD4 genome AF: 0.00103 AC: 157 AN: 151898 Hom.: 1 Cov.: 31 AF XY: 0.00132 AC XY: 98 AN XY: 74230

Gnomad4 AFR AF: 0.000266

Gnomad4 AMR AF: 0.000197

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0224

Gnomad4 SAS AF: 0.00436

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.00190

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.2
DANN	Benign	0.60

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: rs4148535; hg19: chr13-95719794;