5-157058359-C-G

Position:

• chr5-157058359-C-G

Variant summary

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

The ENST00000339252.8(HAVCR1):​c.-416G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.508 in 158,890 control chromosomes in the GnomAD database, including 20,747 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 0.51 (19725 hom., cov: 32)
  • Exomes 𝑓: 0.53 (1022 hom.)
• Consequence: HAVCR1 ENST00000339252.8 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.272

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.632 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HAVCR1	NM_001173393.3	c.-12-404G>C		intron_variant		ENST00000523175.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HAVCR1	ENST00000523175.6	c.-12-404G>C		intron_variant		1	NM_001173393.3	P2

Frequencies

GnomAD3 genomes AF: 0.507 AC: 76947 AN: 151866 Hom.: 19710 Cov.: 32

Gnomad AFR AF: 0.426

Gnomad AMI AF: 0.767

Gnomad AMR AF: 0.515

Gnomad ASJ AF: 0.611

Gnomad EAS AF: 0.651

Gnomad SAS AF: 0.627

Gnomad FIN AF: 0.466

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.531

Gnomad OTH AF: 0.522

GnomAD4 exome AF: 0.535 AC: 3693 AN: 6906 Hom.: 1022 Cov.: 0 AF XY: 0.531 AC XY: 1930 AN XY: 3634

Gnomad4 AFR exome AF: 0.418

Gnomad4 AMR exome AF: 0.435

Gnomad4 ASJ exome AF: 0.671

Gnomad4 EAS exome AF: 0.715

Gnomad4 SAS exome AF: 0.607

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.532

Gnomad4 OTH exome AF: 0.503

GnomAD4 genome AF: 0.507 AC: 77005 AN: 151984 Hom.: 19725 Cov.: 32 AF XY: 0.507 AC XY: 37678 AN XY: 74272

Gnomad4 AFR AF: 0.426

Gnomad4 AMR AF: 0.515

Gnomad4 ASJ AF: 0.611

Gnomad4 EAS AF: 0.650

Gnomad4 SAS AF: 0.626

Gnomad4 FIN AF: 0.466

Gnomad4 NFE AF: 0.531

Gnomad4 OTH AF: 0.527

Alfa AF: 0.374 Hom.: 959

Bravo AF: 0.501

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.8
DANN	Benign	0.81

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: rs9313422; hg19: chr5-156485370; COSMIC: COSV59398738;