chr13-95164453-G-A

Variant names:

• chr13-95164453-G-A
• rs11568666
• NM_005845.5:c.2100C>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_005845.5(ABCC4):​c.2100C>T​(p.Ala700Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00755 in 1,614,150 control chromosomes in the GnomAD database, including 66 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0058 (5 hom., cov: 32)
  • Exomes 𝑓: 0.0077 (61 hom.)
• Consequence: ABCC4 NM_005845.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.438
• Publications: 7 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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant 13-95164453-G-A is Benign according to our data. Variant chr13-95164453-G-A is described in ClinVar as Benign. ClinVar VariationId is 779444.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.438 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

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.2100C>T	p.Ala700Ala	synonymous	Exon 16 of 31	NP_005836.2
	ABCC4	NM_001105515.3		c.2100C>T	p.Ala700Ala	synonymous	Exon 16 of 21	NP_001098985.1
	ABCC4	NM_001301830.2		c.1875C>T	p.Ala625Ala	synonymous	Exon 15 of 20	NP_001288759.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC4	ENST00000645237.2	MANE Select	c.2100C>T	p.Ala700Ala	synonymous	Exon 16 of 31	ENSP00000494609.1
	ABCC4	ENST00000629385.1	TSL:1	c.2100C>T	p.Ala700Ala	synonymous	Exon 16 of 21	ENSP00000487081.1
	ABCC4	ENST00000536256.3	TSL:2	c.1875C>T	p.Ala625Ala	synonymous	Exon 15 of 20	ENSP00000442024.1

Frequencies

GnomAD3 genomes AF: 0.00583 AC: 887 AN: 152208 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.00135

Gnomad AMI AF: 0.0471

Gnomad AMR AF: 0.00334

Gnomad ASJ AF: 0.0311

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0128

Gnomad FIN AF: 0.00179

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00782

Gnomad OTH AF: 0.00621

GnomAD2 exomes AF: 0.00688 AC: 1728 AN: 251270 AF XY: 0.00713

Gnomad AFR exome AF: 0.00105

Gnomad AMR exome AF: 0.00240

Gnomad ASJ exome AF: 0.0273

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00393

Gnomad NFE exome AF: 0.00768

Gnomad OTH exome AF: 0.00767

GnomAD4 exome AF: 0.00772 AC: 11292 AN: 1461824 Hom.: 61 Cov.: 31 AF XY: 0.00790 AC XY: 5745 AN XY: 727210

African (AFR) AF: 0.000896 AC: 30 AN: 33480

American (AMR) AF: 0.00277 AC: 124 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0288 AC: 752 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.0112 AC: 965 AN: 86258

European-Finnish (FIN) AF: 0.00384 AC: 205 AN: 53418

Middle Eastern (MID) AF: 0.00988 AC: 57 AN: 5768

European-Non Finnish (NFE) AF: 0.00773 AC: 8600 AN: 1111964

Other (OTH) AF: 0.00926 AC: 559 AN: 60394

GnomAD4 genome AF: 0.00583 AC: 888 AN: 152326 Hom.: 5 Cov.: 32 AF XY: 0.00583 AC XY: 434 AN XY: 74484

African (AFR) AF: 0.00135 AC: 56 AN: 41574

American (AMR) AF: 0.00333 AC: 51 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0311 AC: 108 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.0131 AC: 63 AN: 4826

European-Finnish (FIN) AF: 0.00179 AC: 19 AN: 10618

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00782 AC: 532 AN: 68028

Other (OTH) AF: 0.00615 AC: 13 AN: 2114

Alfa AF: 0.00792 Hom.: 20

Bravo AF: 0.00594

Asia WGS AF: 0.00375 AC: 13 AN: 3478

EpiCase AF: 0.00851

EpiControl AF: 0.00771

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Aug 28, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	9.4
DANN	Benign	0.58
PhyloP100		0.44
Mutation Taster		=100/0	polymorphism

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: rs11568666; hg19: chr13-95816707;