rs1189451

Positions:

• chr13-95069832-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005845.5(ABCC4):​c.3210+1830C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.74 in 152,172 control chromosomes in the GnomAD database, including 42,674 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 0.74 (42674 hom., cov: 32)
• Consequence: ABCC4 NM_005845.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.545

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.877 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCC4	NM_005845.5	c.3210+1830C>T		intron_variant		ENST00000645237.2	NP_005836.2
ABCC4	NM_001301829.2	c.3069+1830C>T		intron_variant			NP_001288758.1
ABCC4	XM_047430034.1	c.3081+1830C>T		intron_variant			XP_047285990.1
ABCC4	XM_047430035.1	c.2661+1830C>T		intron_variant			XP_047285991.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCC4	ENST00000645237.2	c.3210+1830C>T		intron_variant			NM_005845.5	ENSP00000494609	P1
ABCC4	ENST00000646439.1	c.3069+1830C>T		intron_variant				ENSP00000494751
ABCC4	ENST00000643051.1	c.*835+1830C>T		intron_variant, NMD_transcript_variant				ENSP00000495513
ABCC4	ENST00000643842.1	c.*3256+1830C>T		intron_variant, NMD_transcript_variant				ENSP00000493861

Frequencies

GnomAD3 genomes AF: 0.740 AC: 112570 AN: 152054 Hom.: 42647 Cov.: 32

Gnomad AFR AF: 0.557

Gnomad AMI AF: 0.726

Gnomad AMR AF: 0.734

Gnomad ASJ AF: 0.743

Gnomad EAS AF: 0.790

Gnomad SAS AF: 0.900

Gnomad FIN AF: 0.847

Gnomad MID AF: 0.791

Gnomad NFE AF: 0.820

Gnomad OTH AF: 0.761

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.740 AC: 112639 AN: 152172 Hom.: 42674 Cov.: 32 AF XY: 0.744 AC XY: 55375 AN XY: 74394

Gnomad4 AFR AF: 0.558

Gnomad4 AMR AF: 0.734

Gnomad4 ASJ AF: 0.743

Gnomad4 EAS AF: 0.791

Gnomad4 SAS AF: 0.900

Gnomad4 FIN AF: 0.847

Gnomad4 NFE AF: 0.820

Gnomad4 OTH AF: 0.764

Alfa AF: 0.792 Hom.: 46443

Bravo AF: 0.721

Asia WGS AF: 0.822 AC: 2862 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.51
DANN	Benign	0.59

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: rs1189451; hg19: chr13-95722086;