13-95061461-G-T

Variant summary

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

The NM_005845.5(ABCC4):c.3366+1243C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 151,958 control chromosomes in the GnomAD database, including 2,485 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 0.17 (2485 hom., cov: 31)
• Consequence: ABCC4 NM_005845.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.10

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 (EAS) allele frequency at 95% confidence interval = 0.27 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCC4	NM_005845.5	c.3366+1243C>A		intron_variant		ENST00000645237.2
ABCC4	NM_001301829.2	c.3225+1243C>A		intron_variant
ABCC4	XM_047430034.1	c.3237+1243C>A		intron_variant
ABCC4	XM_047430035.1	c.2817+1243C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCC4	ENST00000645237.2	c.3366+1243C>A		intron_variant			NM_005845.5	P1
ABCC4	ENST00000646439.1	c.3225+1243C>A		intron_variant
ABCC4	ENST00000643051.1	c.*991+1243C>A		intron_variant, NMD_transcript_variant
ABCC4	ENST00000643842.1	c.*3412+1243C>A		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.175 AC: 26532 AN: 151840 Hom.: 2476 Cov.: 31

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.121

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.281

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.158

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.143

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

GnomAD4 genome AF: 0.175 AC: 26578 AN: 151958 Hom.: 2485 Cov.: 31 AF XY: 0.171 AC XY: 12706 AN XY: 74254

Gnomad4 AFR AF: 0.145

Gnomad4 AMR AF: 0.121

Gnomad4 ASJ AF: 0.116

Gnomad4 EAS AF: 0.282

Gnomad4 SAS AF: 0.153

Gnomad4 FIN AF: 0.158

Gnomad4 NFE AF: 0.206

Gnomad4 OTH AF: 0.148

Alfa AF: 0.179 Hom.: 3002

Bravo AF: 0.171

Asia WGS AF: 0.206 AC: 718 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	0.074
Dann	Benign	0.68

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: rs9561778; hg19: chr13-95713715;