chr5-157042772-G-A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000523175.6(HAVCR1):​c.782-90C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 775,520 control chromosomes in the GnomAD database, including 10,698 homozygotes. 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: 𝑓 0.16 (2124 hom., cov: 33)
  • Exomes 𝑓: 0.16 (8574 hom.)
• Consequence: HAVCR1 ENST00000523175.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0230
• Publications: 9 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.

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>T		intron	N/A	NP_001166864.1
	HAVCR1	NM_001308156.2		c.782-90C>T		intron	N/A	NP_001295085.1
	HAVCR1	NM_012206.3		c.782-90C>T		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>T		intron	N/A	ENSP00000427898.1
	HAVCR1	ENST00000339252.8	TSL:1	c.782-90C>T		intron	N/A	ENSP00000344844.3
	HAVCR1	ENST00000522693.5	TSL:2	c.782-90C>T		intron	N/A	ENSP00000428524.1

Frequencies

GnomAD3 genomes AF: 0.164 AC: 24928 AN: 151998 Hom.: 2127 Cov.: 33

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.151

Gnomad AMR AF: 0.161

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.124

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.150

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.169

Gnomad OTH AF: 0.171

GnomAD4 exome AF: 0.160 AC: 99922 AN: 623404 Hom.: 8574 AF XY: 0.161 AC XY: 54068 AN XY: 334816

African (AFR) AF: 0.170 AC: 2642 AN: 15580

American (AMR) AF: 0.0992 AC: 3012 AN: 30350

Ashkenazi Jewish (ASJ) AF: 0.240 AC: 4450 AN: 18566

East Asian (EAS) AF: 0.0918 AC: 2998 AN: 32664

South Asian (SAS) AF: 0.154 AC: 8668 AN: 56146

European-Finnish (FIN) AF: 0.157 AC: 7235 AN: 46194

Middle Eastern (MID) AF: 0.268 AC: 868 AN: 3236

European-Non Finnish (NFE) AF: 0.166 AC: 64396 AN: 388770

Other (OTH) AF: 0.177 AC: 5653 AN: 31898

GnomAD4 genome AF: 0.164 AC: 24931 AN: 152116 Hom.: 2124 Cov.: 33 AF XY: 0.163 AC XY: 12091 AN XY: 74348

African (AFR) AF: 0.161 AC: 6695 AN: 41490

American (AMR) AF: 0.161 AC: 2455 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.241 AC: 835 AN: 3470

East Asian (EAS) AF: 0.123 AC: 636 AN: 5162

South Asian (SAS) AF: 0.141 AC: 680 AN: 4826

European-Finnish (FIN) AF: 0.150 AC: 1580 AN: 10560

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.169 AC: 11463 AN: 68008

Other (OTH) AF: 0.171 AC: 362 AN: 2112

Alfa AF: 0.167 Hom.: 2521

Bravo AF: 0.164

Asia WGS AF: 0.144 AC: 501 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	11
DANN	Benign	0.73
PhyloP100		-0.023
Mutation Taster		=100/0	polymorphism (auto)

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; COSMIC: COSV59399575;