5-157052557-C-CGTT

Variant names:

• chr5-157052557-C-CGTT
• rs77147640
• NM_001173393.3:c.476_477insAAC

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 1P and 8B. PM4_Supporting BP6_Very_Strong

The NM_001173393.3(HAVCR1):​c.476_477insAAC​(p.Thr159dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.59 (9303 hom., cov: 0)
  • Exomes 𝑓: 0.54 (44250 hom.)
  • Failed GnomAD Quality Control
• Consequence: HAVCR1 NM_001173393.3 disruptive_inframe_insertion
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.344
• Publications: 8 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 -7 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_001173393.3. Strenght limited to Supporting due to length of the change: 1aa.
• BP6: Variant 5-157052557-C-CGTT is Benign according to our data. Variant chr5-157052557-C-CGTT is described in ClinVar as [Benign]. Clinvar id is 402920.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HAVCR1	NM_001173393.3	c.476_477insAAC	p.Thr159dup	disruptive_inframe_insertion	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.476_477insAAC	p.Thr159dup	disruptive_inframe_insertion	Exon 4 of 9	1	NM_001173393.3	ENSP00000427898.1

Frequencies

GnomAD3 genomes AF: 0.589 AC: 48287 AN: 82032 Hom.: 9285 Cov.: 0

Gnomad AFR AF: 0.656

Gnomad AMI AF: 0.573

Gnomad AMR AF: 0.557

Gnomad ASJ AF: 0.589

Gnomad EAS AF: 0.557

Gnomad SAS AF: 0.571

Gnomad FIN AF: 0.516

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.532

Gnomad OTH AF: 0.574

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.541 AC: 347235 AN: 641254 Hom.: 44250 Cov.: 0 AF XY: 0.543 AC XY: 173656 AN XY: 319682

African (AFR) AF: 0.664 AC: 18696 AN: 28142

American (AMR) AF: 0.537 AC: 7134 AN: 13278

Ashkenazi Jewish (ASJ) AF: 0.588 AC: 8582 AN: 14588

East Asian (EAS) AF: 0.545 AC: 6250 AN: 11478

South Asian (SAS) AF: 0.580 AC: 23203 AN: 39986

European-Finnish (FIN) AF: 0.518 AC: 10331 AN: 19936

Middle Eastern (MID) AF: 0.619 AC: 2348 AN: 3794

European-Non Finnish (NFE) AF: 0.529 AC: 254586 AN: 481060

Other (OTH) AF: 0.555 AC: 16105 AN: 28992

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.589 AC: 48342 AN: 82112 Hom.: 9303 Cov.: 0 AF XY: 0.587 AC XY: 23244 AN XY: 39608

African (AFR) AF: 0.656 AC: 22345 AN: 34062

American (AMR) AF: 0.557 AC: 3876 AN: 6964

Ashkenazi Jewish (ASJ) AF: 0.589 AC: 1153 AN: 1958

East Asian (EAS) AF: 0.558 AC: 1026 AN: 1838

South Asian (SAS) AF: 0.572 AC: 1224 AN: 2140

European-Finnish (FIN) AF: 0.516 AC: 1947 AN: 3774

Middle Eastern (MID) AF: 0.638 AC: 125 AN: 196

European-Non Finnish (NFE) AF: 0.532 AC: 15781 AN: 29672

Other (OTH) AF: 0.574 AC: 653 AN: 1138

Alfa AF: 0.295 Hom.: 466

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Does not pass quality filter -

not provided Benign:1

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.34
Mutation Taster		=87/13	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs77147640; hg19: chr5-156479568; COSMIC: COSV59397309; COSMIC: COSV59397309;