5-157052546-GTTGGAACAGTCGTCA-G

Position:

• chr5-157052546-GTTGGAACAGTCGTCA-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM4 BP6_Moderate BA1

The NM_001173393.3(HAVCR1):​c.473_487del​(p.Met158_Pro162del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.619 in 1,593,314 control chromosomes in the GnomAD database, including 307,636 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.62 (24413 hom., cov: 0)
  • Exomes 𝑓: 0.62 (283223 hom.)
• Consequence: HAVCR1 NM_001173393.3 inframe_deletion
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.28

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.

• PM4: Nonframeshift variant in NON repetitive region in NM_001173393.3.
• BP6: Variant 5-157052546-GTTGGAACAGTCGTCA-G is Benign according to our data. Variant chr5-157052546-GTTGGAACAGTCGTCA-G is described in ClinVar as [Benign]. Clinvar id is 769670.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.8 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HAVCR1	NM_001173393.3	c.473_487del	p.Met158_Pro162del	inframe_deletion	4/9	ENST00000523175.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HAVCR1	ENST00000523175.6	c.473_487del	p.Met158_Pro162del	inframe_deletion	4/9	1	NM_001173393.3	P2

Frequencies

GnomAD3 genomes AF: 0.622 AC: 83345 AN: 133918 Hom.: 24396 Cov.: 0

Gnomad AFR AF: 0.467

Gnomad AMI AF: 0.795

Gnomad AMR AF: 0.703

Gnomad ASJ AF: 0.639

Gnomad EAS AF: 0.820

Gnomad SAS AF: 0.747

Gnomad FIN AF: 0.695

Gnomad MID AF: 0.534

Gnomad NFE AF: 0.638

Gnomad OTH AF: 0.628

GnomAD3 exomes AF: 0.639 AC: 159499 AN: 249512 Hom.: 52698 AF XY: 0.640 AC XY: 86593 AN XY: 135376

Gnomad AFR exome AF: 0.331

Gnomad AMR exome AF: 0.784

Gnomad ASJ exome AF: 0.576

Gnomad EAS exome AF: 0.784

Gnomad SAS exome AF: 0.688

Gnomad FIN exome AF: 0.652

Gnomad NFE exome AF: 0.606

Gnomad OTH exome AF: 0.606

GnomAD4 exome AF: 0.619 AC: 903147 AN: 1459302 Hom.: 283223 AF XY: 0.620 AC XY: 450358 AN XY: 725954

Gnomad4 AFR exome AF: 0.321

Gnomad4 AMR exome AF: 0.773

Gnomad4 ASJ exome AF: 0.577

Gnomad4 EAS exome AF: 0.825

Gnomad4 SAS exome AF: 0.687

Gnomad4 FIN exome AF: 0.653

Gnomad4 NFE exome AF: 0.610

Gnomad4 OTH exome AF: 0.599

GnomAD4 genome AF: 0.622 AC: 83398 AN: 134012 Hom.: 24413 Cov.: 0 AF XY: 0.630 AC XY: 41386 AN XY: 65712

Gnomad4 AFR AF: 0.467

Gnomad4 AMR AF: 0.704

Gnomad4 ASJ AF: 0.639

Gnomad4 EAS AF: 0.821

Gnomad4 SAS AF: 0.747

Gnomad4 FIN AF: 0.695

Gnomad4 NFE AF: 0.638

Gnomad4 OTH AF: 0.628

Alfa AF: 0.505 Hom.: 2559

Asia WGS AF: 0.700 AC: 2429 AN: 3470

EpiCase AF: 0.596

EpiControl AF: 0.591

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs6149307; hg19: chr5-156479557;