rs11568652

chr13-95062815-G-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_005845.5(ABCC4):c.3255C>A(p.Ile1085=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000341 in 1,613,612 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0016 (2 hom., cov: 30)
  • Exomes 𝑓: 0.00021 (2 hom.)
• Consequence: ABCC4 NM_005845.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.237

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant 13-95062815-G-T is Benign according to our data. Variant chr13-95062815-G-T is described in ClinVar as [Benign]. Clinvar id is 726207.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.237 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCC4	NM_005845.5	c.3255C>A	p.Ile1085=	synonymous_variant	26/31	ENST00000645237.2
ABCC4	NM_001301829.2	c.3114C>A	p.Ile1038=	synonymous_variant	25/30
ABCC4	XM_047430034.1	c.3126C>A	p.Ile1042=	synonymous_variant	26/31
ABCC4	XM_047430035.1	c.2706C>A	p.Ile902=	synonymous_variant	23/28

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCC4	ENST00000645237.2	c.3255C>A	p.Ile1085=	synonymous_variant	26/31		NM_005845.5	P1
ABCC4	ENST00000646439.1	c.3114C>A	p.Ile1038=	synonymous_variant	25/30
ABCC4	ENST00000643051.1	c.*880C>A		3_prime_UTR_variant, NMD_transcript_variant	27/33
ABCC4	ENST00000643842.1	c.*3301C>A		3_prime_UTR_variant, NMD_transcript_variant	27/32

Frequencies

GnomAD3 genomes AF: 0.00160 AC: 243 AN: 151718 Hom.: 2 Cov.: 30

Gnomad AFR AF: 0.00562

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000526

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.000480

GnomAD3 exomes AF: 0.000438 AC: 110 AN: 251286 Hom.: 0 AF XY: 0.000375 AC XY: 51 AN XY: 135822

Gnomad AFR exome AF: 0.00585

Gnomad AMR exome AF: 0.000174

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000440

Gnomad OTH exome AF: 0.000653

GnomAD4 exome AF: 0.000209 AC: 305 AN: 1461776 Hom.: 2 Cov.: 38 AF XY: 0.000202 AC XY: 147 AN XY: 727184

Gnomad4 AFR exome AF: 0.00672

Gnomad4 AMR exome AF: 0.000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000252

Gnomad4 OTH exome AF: 0.000613

GnomAD4 genome AF: 0.00162 AC: 246 AN: 151836 Hom.: 2 Cov.: 30 AF XY: 0.00142 AC XY: 105 AN XY: 74144

Gnomad4 AFR AF: 0.00567

Gnomad4 AMR AF: 0.000525

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.000475

Alfa AF: 0.000469 Hom.: 1

Bravo AF: 0.00178

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 13, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
Cadd	Benign	3.3
Dann	Benign	0.71

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

Publications

LitVar

Other links and lift over

dbSNP: rs11568652; hg19: chr13-95715069;