rs34333511

Positions:

• chr5-157058357-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000339252.8(HAVCR1):​c.-414T>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0124 in 161,730 control chromosomes in the GnomAD database, including 13 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 0.013 (12 hom., cov: 33)
  • Exomes 𝑓: 0.0065 (1 hom.)
• Consequence: HAVCR1 ENST00000339252.8 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.793

Genes affected

HAVCR1 (HGNC:17866): (hepatitis A virus cellular receptor 1) The protein encoded by this gene is a membrane receptor for both human hepatitis A virus (HHAV) and TIMD4. The encoded protein may be involved in the moderation of asthma and allergic diseases. The reference genome represents an allele that retains a MTTVP amino acid segment that confers protection against atopy in HHAV seropositive individuals. The protein is a receptor for multiple other viruses, including Ebola virus, Marburg virus, Dengue virus, and Zika virus and is a possible entry factor for SARS-CoV-2 and other coronaviruses. [provided by RefSeq, Sep 2021]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0128 (1944/152292) while in subpopulation AFR AF= 0.0209 (869/41576). AF 95% confidence interval is 0.0197. There are 12 homozygotes in gnomad4. There are 907 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HAVCR1	NM_001173393.3	c.-12-402T>A		intron_variant		ENST00000523175.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HAVCR1	ENST00000523175.6	c.-12-402T>A		intron_variant		1	NM_001173393.3	P2

Frequencies

GnomAD3 genomes AF: 0.0127 AC: 1940 AN: 152174 Hom.: 12 Cov.: 33

Gnomad AFR AF: 0.0209

Gnomad AMI AF: 0.0462

Gnomad AMR AF: 0.00995

Gnomad ASJ AF: 0.00519

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00443

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0115

Gnomad OTH AF: 0.0129

GnomAD4 exome AF: 0.00646 AC: 61 AN: 9438 Hom.: 1 Cov.: 0 AF XY: 0.00543 AC XY: 27 AN XY: 4968

Gnomad4 AFR exome AF: 0.0307

Gnomad4 AMR exome AF: 0.00521

Gnomad4 ASJ exome AF: 0.00442

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00286

Gnomad4 NFE exome AF: 0.00698

Gnomad4 OTH exome AF: 0.0112

GnomAD4 genome AF: 0.0128 AC: 1944 AN: 152292 Hom.: 12 Cov.: 33 AF XY: 0.0122 AC XY: 907 AN XY: 74458

Gnomad4 AFR AF: 0.0209

Gnomad4 AMR AF: 0.00987

Gnomad4 ASJ AF: 0.00519

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00124

Gnomad4 FIN AF: 0.00443

Gnomad4 NFE AF: 0.0115

Gnomad4 OTH AF: 0.0147

Alfa AF: 0.0128 Hom.: 1

Bravo AF: 0.0130

Asia WGS AF: 0.00404 AC: 14 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.9
DANN	Benign	0.84

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: rs34333511; hg19: chr5-156485368;