13-95021537-A-C

Variant names:

• chr13-95021537-A-C
• rs3742106
• NM_005845.5:c.*38T>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.*38T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.403 in 1,474,528 control chromosomes in the GnomAD database, including 121,508 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 0.38 (11040 hom., cov: 32)
  • Exomes 𝑓: 0.41 (110468 hom.)
• Consequence: ABCC4 NM_005845.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.179
• Publications: 56 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.48 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005845.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC4	NM_005845.5	MANE Select	c.*38T>G		3_prime_UTR	Exon 31 of 31	NP_005836.2
	ABCC4	NM_001301829.2		c.*38T>G		3_prime_UTR	Exon 30 of 30	NP_001288758.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC4	ENST00000645237.2	MANE Select	c.*38T>G		3_prime_UTR	Exon 31 of 31	ENSP00000494609.1
	ABCC4	ENST00000643051.1		n.*1927T>G		non_coding_transcript_exon	Exon 33 of 33	ENSP00000495513.1
	ABCC4	ENST00000643842.1		n.*4062T>G		non_coding_transcript_exon	Exon 32 of 32	ENSP00000493861.1

Frequencies

GnomAD3 genomes AF: 0.379 AC: 57546 AN: 151954 Hom.: 11040 Cov.: 32

Gnomad AFR AF: 0.324

Gnomad AMI AF: 0.325

Gnomad AMR AF: 0.428

Gnomad ASJ AF: 0.352

Gnomad EAS AF: 0.495

Gnomad SAS AF: 0.479

Gnomad FIN AF: 0.322

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.395

Gnomad OTH AF: 0.396

GnomAD2 exomes AF: 0.410 AC: 99007 AN: 241270 AF XY: 0.413

Gnomad AFR exome AF: 0.322

Gnomad AMR exome AF: 0.467

Gnomad ASJ exome AF: 0.352

Gnomad EAS exome AF: 0.512

Gnomad FIN exome AF: 0.329

Gnomad NFE exome AF: 0.390

Gnomad OTH exome AF: 0.403

GnomAD4 exome AF: 0.406 AC: 536675 AN: 1322456 Hom.: 110468 Cov.: 20 AF XY: 0.408 AC XY: 271112 AN XY: 664278

African (AFR) AF: 0.325 AC: 9788 AN: 30154

American (AMR) AF: 0.459 AC: 19578 AN: 42642

Ashkenazi Jewish (ASJ) AF: 0.350 AC: 8786 AN: 25106

East Asian (EAS) AF: 0.498 AC: 19428 AN: 38994

South Asian (SAS) AF: 0.489 AC: 39495 AN: 80718

European-Finnish (FIN) AF: 0.330 AC: 17561 AN: 53174

Middle Eastern (MID) AF: 0.423 AC: 2325 AN: 5494

European-Non Finnish (NFE) AF: 0.401 AC: 397154 AN: 990310

Other (OTH) AF: 0.404 AC: 22560 AN: 55864

GnomAD4 genome AF: 0.379 AC: 57567 AN: 152072 Hom.: 11040 Cov.: 32 AF XY: 0.377 AC XY: 28044 AN XY: 74308

African (AFR) AF: 0.324 AC: 13449 AN: 41492

American (AMR) AF: 0.427 AC: 6529 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.352 AC: 1219 AN: 3466

East Asian (EAS) AF: 0.496 AC: 2563 AN: 5170

South Asian (SAS) AF: 0.478 AC: 2306 AN: 4822

European-Finnish (FIN) AF: 0.322 AC: 3402 AN: 10564

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.395 AC: 26835 AN: 67968

Other (OTH) AF: 0.400 AC: 843 AN: 2110

Alfa AF: 0.391 Hom.: 44345

Bravo AF: 0.385

Asia WGS AF: 0.484 AC: 1682 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.8
DANN	Benign	0.49
PhyloP100		0.18
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs3742106; hg19: chr13-95673791; COSMIC: COSV65316236; COSMIC: COSV65316236;