chr13-95020203-T-G

Variant names:

• chr13-95020203-T-G
• rs9516519
• NM_005845.5:c.*1372A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 19 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=-0.81).
• 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 rank	MANE	Protein	UniProt
ABCC4	NM_005845.5	c.*1372A>C		3_prime_UTR_variant	Exon 31 of 31	ENST00000645237.2	NP_005836.2
ABCC4	NM_001301829.2	c.*1372A>C		3_prime_UTR_variant	Exon 30 of 30		NP_001288758.1
ABCC4	XM_047430034.1	c.*1372A>C		3_prime_UTR_variant	Exon 31 of 31		XP_047285990.1
ABCC4	XM_047430035.1	c.*1372A>C		3_prime_UTR_variant	Exon 28 of 28		XP_047285991.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC4	ENST00000645237.2	c.*1372A>C		3_prime_UTR_variant	Exon 31 of 31		NM_005845.5	ENSP00000494609.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.0266 AC: 1104 AN: 41574

American (AMR) AF: 0.163 AC: 2497 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.203 AC: 703 AN: 3470

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5190

South Asian (SAS) AF: 0.0360 AC: 174 AN: 4828

European-Finnish (FIN) AF: 0.0735 AC: 780 AN: 10616

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.139 AC: 9481 AN: 67994

Other (OTH) AF: 0.122 AC: 257 AN: 2110

Alfa AF: 0.130 Hom.: 4896

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
PhyloP100		-0.22
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: rs9516519; hg19: chr13-95672457;