rs3770

chr13-95019983-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.*1592C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.416 in 152,096 control chromosomes in the GnomAD database, including 13,264 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 0.42 (13264 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: ABCC4 NM_005845.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0900

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.481 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCC4	NM_005845.5	c.*1592C>T		3_prime_UTR_variant	31/31	ENST00000645237.2
ABCC4	NM_001301829.2	c.*1592C>T		3_prime_UTR_variant	30/30
ABCC4	XM_047430034.1	c.*1592C>T		3_prime_UTR_variant	31/31
ABCC4	XM_047430035.1	c.*1592C>T		3_prime_UTR_variant	28/28

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCC4	ENST00000645237.2	c.*1592C>T		3_prime_UTR_variant	31/31		NM_005845.5	P1
ABCC4	ENST00000643051.1	c.*3481C>T		3_prime_UTR_variant, NMD_transcript_variant	33/33
ABCC4	ENST00000643842.1	c.*5616C>T		3_prime_UTR_variant, NMD_transcript_variant	32/32

Frequencies

GnomAD3 genomes AF: 0.416 AC: 63227 AN: 151978 Hom.: 13259 Cov.: 33

Gnomad AFR AF: 0.433

Gnomad AMI AF: 0.327

Gnomad AMR AF: 0.444

Gnomad ASJ AF: 0.354

Gnomad EAS AF: 0.496

Gnomad SAS AF: 0.483

Gnomad FIN AF: 0.331

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.406

Gnomad OTH AF: 0.421

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.416 AC: 63267 AN: 152096 Hom.: 13264 Cov.: 33 AF XY: 0.414 AC XY: 30807 AN XY: 74334

Gnomad4 AFR AF: 0.433

Gnomad4 AMR AF: 0.443

Gnomad4 ASJ AF: 0.354

Gnomad4 EAS AF: 0.497

Gnomad4 SAS AF: 0.483

Gnomad4 FIN AF: 0.331

Gnomad4 NFE AF: 0.405

Gnomad4 OTH AF: 0.425

Alfa AF: 0.402 Hom.: 5735

Bravo AF: 0.425

Asia WGS AF: 0.489 AC: 1702 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	2.5
Dann	Benign	0.65
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs3770; hg19: chr13-95672237;