rs756372983

Variant names:

• chr13-95021657-T-A
• rs756372983
• NM_005845.5:c.3896A>T

Your query was ambiguous. Multiple possible variants found:

• chr13-95021657-T-A
• chr13-95021657-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005845.5(ABCC4):​c.3896A>T​(p.His1299Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H1299R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ABCC4 NM_005845.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.15

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06459308).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC4	NM_005845.5	c.3896A>T	p.His1299Leu	missense_variant	Exon 31 of 31	ENST00000645237.2	NP_005836.2
ABCC4	NM_001301829.2	c.3755A>T	p.His1252Leu	missense_variant	Exon 30 of 30		NP_001288758.1
ABCC4	XM_047430034.1	c.3767A>T	p.His1256Leu	missense_variant	Exon 31 of 31		XP_047285990.1
ABCC4	XM_047430035.1	c.3347A>T	p.His1116Leu	missense_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.3896A>T	p.His1299Leu	missense_variant	Exon 31 of 31		NM_005845.5	ENSP00000494609.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.047	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	11
DANN	Benign	0.65
DEOGEN2	Benign	0.078	T;T;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.46	.;T;T
M_CAP	Benign	0.046	D
MetaRNN	Benign	0.065	T;T;T
MetaSVM	Benign	-0.75	T
MutationAssessor	Benign	-0.46	N;N;.
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.88	.;N;.
REVEL	Benign	0.26
Sift	Benign	0.17	.;T;.
Sift4G	Benign	0.26	.;T;.
Polyphen		0.0040	B;B;B
Vest4		0.12
MutPred		0.41		Loss of disorder (P = 0.0475);Loss of disorder (P = 0.0475);.;
MVP		0.51
MPC		0.29
ClinPred		0.081	T
GERP RS		1.5
Varity_R		0.056
gMVP		0.58

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

Publications

LitVar

Other links and lift over

dbSNP: rs756372983; hg19: chr13-95673911;