rs6149307

Variant names:

• chr5-157052546-GTTGGAACAGTCGTCA-G
• rs6149307
• NM_001173393.3:c.473_487delTGACGACTGTTCCAA

Your query was ambiguous. Multiple possible variants found:

• chr5-157052546-GTTGGAACAGTCGTCA-G
• chr5-157052546-GTTGGAACAGTCGTCA-GTTGGAACAGTCGTCATTGGAACAGTCGTCA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 2P and 10B. PM4 BP6_Moderate BA1

The NM_001173393.3(HAVCR1):​c.473_487delTGACGACTGTTCCAA​(p.Met158_Pro162del) variant causes a disruptive 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. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. 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 disruptive_inframe_deletion
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.28
• Publications: 13 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
HAVCR1	NM_001173393.3	c.473_487delTGACGACTGTTCCAA	p.Met158_Pro162del	disruptive_inframe_deletion	Exon 4 of 9	ENST00000523175.6	NP_001166864.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HAVCR1	ENST00000523175.6	c.473_487delTGACGACTGTTCCAA	p.Met158_Pro162del	disruptive_inframe_deletion	Exon 4 of 9	1	NM_001173393.3	ENSP00000427898.1

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

GnomAD2 exomes AF: 0.639 AC: 159499 AN: 249512 AF XY: 0.640

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 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

African (AFR) AF: 0.321 AC: 10672 AN: 33226

American (AMR) AF: 0.773 AC: 34536 AN: 44658

Ashkenazi Jewish (ASJ) AF: 0.577 AC: 15041 AN: 26066

East Asian (EAS) AF: 0.825 AC: 32715 AN: 39662

South Asian (SAS) AF: 0.687 AC: 59063 AN: 86026

European-Finnish (FIN) AF: 0.653 AC: 34843 AN: 53378

Middle Eastern (MID) AF: 0.471 AC: 2711 AN: 5756

European-Non Finnish (NFE) AF: 0.610 AC: 677474 AN: 1110230

Other (OTH) AF: 0.599 AC: 36092 AN: 60300

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

African (AFR) AF: 0.467 AC: 13881 AN: 29744

American (AMR) AF: 0.704 AC: 9999 AN: 14206

Ashkenazi Jewish (ASJ) AF: 0.639 AC: 1990 AN: 3116

East Asian (EAS) AF: 0.821 AC: 4059 AN: 4944

South Asian (SAS) AF: 0.747 AC: 3342 AN: 4472

European-Finnish (FIN) AF: 0.695 AC: 7080 AN: 10188

Middle Eastern (MID) AF: 0.537 AC: 130 AN: 242

European-Non Finnish (NFE) AF: 0.638 AC: 41048 AN: 64352

Other (OTH) AF: 0.628 AC: 1190 AN: 1894

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

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.3
Mutation Taster		=197/3	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs6149307; hg19: chr5-156479557; COSMIC: COSV59397359; COSMIC: COSV59397359;