rs34819868

Positions:

• chr5-157058365-C-A
• chr5-157058365-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The ENST00000339252.8(HAVCR1):​c.-422G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0069 in 158,408 control chromosomes in the GnomAD database, including 4 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 0.0069 (3 hom., cov: 33)
  • Exomes 𝑓: 0.0059 (1 hom.)
• Consequence: HAVCR1 ENST00000339252.8 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.461

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HAVCR1	NM_001173393.3	c.-12-410G>T		intron_variant		ENST00000523175.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HAVCR1	ENST00000523175.6	c.-12-410G>T		intron_variant		1	NM_001173393.3	P2

Frequencies

GnomAD3 genomes AF: 0.00693 AC: 1054 AN: 152162 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.00224

Gnomad AMI AF: 0.0462

Gnomad AMR AF: 0.00583

Gnomad ASJ AF: 0.00519

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00405

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0111

Gnomad OTH AF: 0.00335

GnomAD4 exome AF: 0.00587 AC: 36 AN: 6128 Hom.: 1 Cov.: 0 AF XY: 0.00483 AC XY: 16 AN XY: 3310

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00345

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00455

Gnomad4 NFE exome AF: 0.00733

Gnomad4 OTH exome AF: 0.0114

GnomAD4 genome AF: 0.00694 AC: 1057 AN: 152280 Hom.: 3 Cov.: 33 AF XY: 0.00619 AC XY: 461 AN XY: 74450

Gnomad4 AFR AF: 0.00224

Gnomad4 AMR AF: 0.00575

Gnomad4 ASJ AF: 0.00519

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00124

Gnomad4 FIN AF: 0.00405

Gnomad4 NFE AF: 0.0111

Gnomad4 OTH AF: 0.00520

Alfa AF: 0.00460 Hom.: 1

Bravo AF: 0.00675

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.4
DANN	Benign	0.85

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: rs34819868; hg19: chr5-156485376;