13-95062760-A-G

Variant names:

• chr13-95062760-A-G
• rs11568655
• NM_005845.5:c.3310T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_005845.5(ABCC4):​c.3310T>C​(p.Leu1104Leu) variant causes a synonymous change. The variant allele was found at a frequency of 0.00502 in 1,614,030 control chromosomes in the GnomAD database, including 335 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 0.026 (188 hom., cov: 30)
  • Exomes 𝑓: 0.0029 (147 hom.)
• Consequence: ABCC4 NM_005845.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.03
• Publications: 8 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0866 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC4	NM_005845.5	MANE Select	c.3310T>C	p.Leu1104Leu	synonymous	Exon 26 of 31	NP_005836.2	O15439-1
	ABCC4	NM_001301829.2		c.3169T>C	p.Leu1057Leu	synonymous	Exon 25 of 30	NP_001288758.1	O15439-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC4	ENST00000645237.2	MANE Select	c.3310T>C	p.Leu1104Leu	synonymous	Exon 26 of 31	ENSP00000494609.1	O15439-1
	ABCC4	ENST00000967420.1		c.3310T>C	p.Leu1104Leu	synonymous	Exon 26 of 31	ENSP00000637479.1
	ABCC4	ENST00000967421.1		c.3307T>C	p.Leu1103Leu	synonymous	Exon 26 of 31	ENSP00000637480.1

Frequencies

GnomAD3 genomes AF: 0.0258 AC: 3924 AN: 152142 Hom.: 188 Cov.: 30

Gnomad AFR AF: 0.0891

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00936

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000720

Gnomad OTH AF: 0.0167

GnomAD2 exomes AF: 0.00655 AC: 1647 AN: 251318 AF XY: 0.00487

Gnomad AFR exome AF: 0.0863

Gnomad AMR exome AF: 0.00463

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000519

Gnomad OTH exome AF: 0.00342

GnomAD4 exome AF: 0.00285 AC: 4170 AN: 1461770 Hom.: 147 Cov.: 38 AF XY: 0.00250 AC XY: 1815 AN XY: 727176

African (AFR) AF: 0.0906 AC: 3030 AN: 33460

American (AMR) AF: 0.00534 AC: 239 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.000220 AC: 19 AN: 86234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00676 AC: 39 AN: 5768

European-Non Finnish (NFE) AF: 0.000449 AC: 499 AN: 1111948

Other (OTH) AF: 0.00568 AC: 343 AN: 60388

GnomAD4 genome AF: 0.0258 AC: 3931 AN: 152260 Hom.: 188 Cov.: 30 AF XY: 0.0258 AC XY: 1922 AN XY: 74456

African (AFR) AF: 0.0890 AC: 3697 AN: 41532

American (AMR) AF: 0.00935 AC: 143 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.000720 AC: 49 AN: 68024

Other (OTH) AF: 0.0166 AC: 35 AN: 2114

Alfa AF: 0.0104 Hom.: 183

Bravo AF: 0.0287

Asia WGS AF: 0.00433 AC: 16 AN: 3478

EpiCase AF: 0.000600

EpiControl AF: 0.000474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	13
DANN	Benign	0.77
PhyloP100		4.0
Mutation Taster		=97/3	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11568655; hg19: chr13-95715014;