ENST00000339252.8:c.-422G>A

Variant names:

• chr5-157058365-C-T
• rs34819868
• ENST00000339252.8:c.-422G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000339252.8(HAVCR1):​c.-422G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HAVCR1 ENST00000339252.8 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.461
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000339252.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HAVCR1	NM_001173393.3	MANE Select	c.-12-410G>A		intron	N/A	NP_001166864.1
	HAVCR1	NM_001308156.2		c.-133-289G>A		intron	N/A	NP_001295085.1
	HAVCR1	NM_012206.3		c.-422G>A		upstream_gene	N/A	NP_036338.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HAVCR1	ENST00000339252.8	TSL:1	c.-422G>A		5_prime_UTR	Exon 1 of 8	ENSP00000344844.3
	HAVCR1	ENST00000523175.6	TSL:1 MANE Select	c.-12-410G>A		intron	N/A	ENSP00000427898.1
	HAVCR1	ENST00000698790.1		c.-74G>A		5_prime_UTR	Exon 1 of 7	ENSP00000513932.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 6128 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 3310

African (AFR) AF: 0.00 AC: 0 AN: 140

American (AMR) AF: 0.00 AC: 0 AN: 580

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 112

East Asian (EAS) AF: 0.00 AC: 0 AN: 254

South Asian (SAS) AF: 0.00 AC: 0 AN: 500

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 220

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 12

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 3958

Other (OTH) AF: 0.00 AC: 0 AN: 352

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.2
DANN	Benign	0.87
PhyloP100		-0.46
PromoterAI		0.031	Neutral

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

Other links and lift over

dbSNP: rs34819868; hg19: chr5-156485376;