13-95067540-G-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005845.5(ABCC4):​c.3210+4122C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 151,832 control chromosomes in the GnomAD database, including 2,871 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 0.19 (2871 hom., cov: 31)
• Consequence: ABCC4 NM_005845.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.316
• Publications: 4 publications found

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]

ABCC4 Gene-Disease associations (from GenCC):

• qualitative platelet defect

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.269 is higher than 0.05.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.189 AC: 28609 AN: 151714 Hom.: 2862 Cov.: 31

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.281

Gnomad SAS AF: 0.158

Gnomad FIN AF: 0.167

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.165

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

GnomAD4 genome AF: 0.189 AC: 28654 AN: 151832 Hom.: 2871 Cov.: 31 AF XY: 0.183 AC XY: 13596 AN XY: 74198

African (AFR) AF: 0.149 AC: 6174 AN: 41406

American (AMR) AF: 0.136 AC: 2080 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 439 AN: 3470

East Asian (EAS) AF: 0.281 AC: 1443 AN: 5134

South Asian (SAS) AF: 0.159 AC: 766 AN: 4814

European-Finnish (FIN) AF: 0.167 AC: 1752 AN: 10520

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.227 AC: 15420 AN: 67930

Other (OTH) AF: 0.169 AC: 356 AN: 2106

Alfa AF: 0.100 Hom.: 166

Bravo AF: 0.186

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.97
DANN	Benign	0.41
PhyloP100		0.32
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4148535; hg19: chr13-95719794;