13-95020203-T-G

Position:

• chr13-95020203-T-G

Variant summary

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

The NM_005845.5(ABCC4):​c.*1372A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0999 in 152,280 control chromosomes in the GnomAD database, including 990 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 0.10 (990 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: ABCC4 NM_005845.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.217

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCC4	NM_005845.5	c.*1372A>C		3_prime_UTR_variant	31/31	ENST00000645237.2
ABCC4	NM_001301829.2	c.*1372A>C		3_prime_UTR_variant	30/30
ABCC4	XM_047430034.1	c.*1372A>C		3_prime_UTR_variant	31/31
ABCC4	XM_047430035.1	c.*1372A>C		3_prime_UTR_variant	28/28

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCC4	ENST00000645237.2	c.*1372A>C		3_prime_UTR_variant	31/31		NM_005845.5	P1
ABCC4	ENST00000643051.1	c.*3261A>C		3_prime_UTR_variant, NMD_transcript_variant	33/33
ABCC4	ENST00000643842.1	c.*5396A>C		3_prime_UTR_variant, NMD_transcript_variant	32/32

Frequencies

GnomAD3 genomes AF: 0.0999 AC: 15203 AN: 152162 Hom.: 987 Cov.: 32

Gnomad AFR AF: 0.0266

Gnomad AMI AF: 0.191

Gnomad AMR AF: 0.163

Gnomad ASJ AF: 0.203

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0356

Gnomad FIN AF: 0.0735

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.123

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.0999 AC: 15213 AN: 152280 Hom.: 990 Cov.: 32 AF XY: 0.0974 AC XY: 7252 AN XY: 74466

Gnomad4 AFR AF: 0.0266

Gnomad4 AMR AF: 0.163

Gnomad4 ASJ AF: 0.203

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0360

Gnomad4 FIN AF: 0.0735

Gnomad4 NFE AF: 0.139

Gnomad4 OTH AF: 0.122

Alfa AF: 0.138 Hom.: 1920

Bravo AF: 0.106

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.4
DANN	Benign	0.63

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: rs9516519; hg19: chr13-95672457;