5-157042772-G-T

Variant names:

• chr5-157042772-G-T
• rs2270926
• NM_001173393.3:c.782-90C>A

Variant summary

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

The ENST00000523175.6(HAVCR1):​c.782-90C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000016 in 624,340 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 0.0000016 (0 hom.)
• Consequence: HAVCR1 ENST00000523175.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0230
• 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=-0.8).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000523175.6. 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.782-90C>A		intron	N/A	NP_001166864.1
	HAVCR1	NM_001308156.2		c.782-90C>A		intron	N/A	NP_001295085.1
	HAVCR1	NM_012206.3		c.782-90C>A		intron	N/A	NP_036338.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HAVCR1	ENST00000523175.6	TSL:1 MANE Select	c.782-90C>A		intron	N/A	ENSP00000427898.1
	HAVCR1	ENST00000339252.8	TSL:1	c.782-90C>A		intron	N/A	ENSP00000344844.3
	HAVCR1	ENST00000522693.5	TSL:2	c.782-90C>A		intron	N/A	ENSP00000428524.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000160 AC: 1 AN: 624340 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 335292

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 15598

American (AMR) AF: 0.00 AC: 0 AN: 30386

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18620

East Asian (EAS) AF: 0.00 AC: 0 AN: 32698

South Asian (SAS) AF: 0.00 AC: 0 AN: 56234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46258

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3240

European-Non Finnish (NFE) AF: 0.00000257 AC: 1 AN: 389350

Other (OTH) AF: 0.00 AC: 0 AN: 31956

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	9.6
DANN	Benign	0.68
PhyloP100		-0.023

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: rs2270926; hg19: chr5-156469783;