chr5-157052546-G-GTTGGAACAGTCGTCA

Variant names:

• chr5-157052546-G-GTTGGAACAGTCGTCA
• rs6149307
• NM_001173393.3:c.473_487dupTGACGACTGTTCCAA

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM4

The NM_001173393.3(HAVCR1):​c.473_487dupTGACGACTGTTCCAA​(p.Met158_Pro162dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.000015 (0 hom., cov: 0)
• Consequence: HAVCR1 NM_001173393.3 conservative_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.595
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_001173393.3.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001173393.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HAVCR1	NM_001173393.3	MANE Select	c.473_487dupTGACGACTGTTCCAA	p.Met158_Pro162dup	conservative_inframe_insertion	Exon 4 of 9	NP_001166864.1	Q96D42
	HAVCR1	NM_001308156.2		c.473_487dupTGACGACTGTTCCAA	p.Met158_Pro162dup	conservative_inframe_insertion	Exon 4 of 8	NP_001295085.1	E9PFX0
	HAVCR1	NM_012206.3		c.473_487dupTGACGACTGTTCCAA	p.Met158_Pro162dup	conservative_inframe_insertion	Exon 3 of 8	NP_036338.2	B4DPB1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HAVCR1	ENST00000523175.6	TSL:1 MANE Select	c.473_487dupTGACGACTGTTCCAA	p.Met158_Pro162dup	conservative_inframe_insertion	Exon 4 of 9	ENSP00000427898.1	Q96D42
	HAVCR1	ENST00000339252.8	TSL:1	c.473_487dupTGACGACTGTTCCAA	p.Met158_Pro162dup	conservative_inframe_insertion	Exon 3 of 8	ENSP00000344844.3	Q96D42
	HAVCR1	ENST00000522693.5	TSL:2	c.473_487dupTGACGACTGTTCCAA	p.Met158_Pro162dup	conservative_inframe_insertion	Exon 4 of 8	ENSP00000428524.1	E9PFX0

Frequencies

GnomAD3 genomes AF: 0.0000149 AC: 2 AN: 134072 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000337

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000533

GnomAD4 exome Cov.: 0

GnomAD4 genome AF: 0.0000149 AC: 2 AN: 134072 Hom.: 0 Cov.: 0 AF XY: 0.0000152 AC XY: 1 AN XY: 65690

African (AFR) AF: 0.0000337 AC: 1 AN: 29694

American (AMR) AF: 0.00 AC: 0 AN: 14210

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3118

East Asian (EAS) AF: 0.00 AC: 0 AN: 4964

South Asian (SAS) AF: 0.00 AC: 0 AN: 4484

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10204

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 262

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 64404

Other (OTH) AF: 0.000533 AC: 1 AN: 1876

Alfa AF: 0.00 Hom.: 2559

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.59
Mutation Taster		=87/13	polymorphism

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;