rs2036402

Positions:

• chr5-157037231-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001173393.3(HAVCR1):​c.952+16A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 1,297,234 control chromosomes in the GnomAD database, including 44,814 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 0.21 (4149 hom., cov: 32)
  • Exomes 𝑓: 0.26 (40665 hom.)
• Consequence: HAVCR1 NM_001173393.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.857

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HAVCR1	NM_001173393.3	c.952+16A>G		intron_variant		ENST00000523175.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HAVCR1	ENST00000523175.6	c.952+16A>G		intron_variant		1	NM_001173393.3	P2

Frequencies

GnomAD3 genomes AF: 0.214 AC: 32535 AN: 151972 Hom.: 4149 Cov.: 32

Gnomad AFR AF: 0.0802

Gnomad AMI AF: 0.282

Gnomad AMR AF: 0.320

Gnomad ASJ AF: 0.273

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.204

Gnomad FIN AF: 0.266

Gnomad MID AF: 0.293

Gnomad NFE AF: 0.265

Gnomad OTH AF: 0.252

GnomAD3 exomes AF: 0.256 AC: 63886 AN: 249154 Hom.: 9284 AF XY: 0.253 AC XY: 34155 AN XY: 135158

Gnomad AFR exome AF: 0.0772

Gnomad AMR exome AF: 0.413

Gnomad ASJ exome AF: 0.270

Gnomad EAS exome AF: 0.136

Gnomad SAS exome AF: 0.205

Gnomad FIN exome AF: 0.253

Gnomad NFE exome AF: 0.265

Gnomad OTH exome AF: 0.275

GnomAD4 exome AF: 0.259 AC: 297022 AN: 1145144 Hom.: 40665 Cov.: 16 AF XY: 0.257 AC XY: 150402 AN XY: 585266

Gnomad4 AFR exome AF: 0.0760

Gnomad4 AMR exome AF: 0.403

Gnomad4 ASJ exome AF: 0.271

Gnomad4 EAS exome AF: 0.121

Gnomad4 SAS exome AF: 0.205

Gnomad4 FIN exome AF: 0.253

Gnomad4 NFE exome AF: 0.271

Gnomad4 OTH exome AF: 0.246

GnomAD4 genome AF: 0.214 AC: 32532 AN: 152090 Hom.: 4149 Cov.: 32 AF XY: 0.214 AC XY: 15888 AN XY: 74322

Gnomad4 AFR AF: 0.0800

Gnomad4 AMR AF: 0.321

Gnomad4 ASJ AF: 0.273

Gnomad4 EAS AF: 0.130

Gnomad4 SAS AF: 0.204

Gnomad4 FIN AF: 0.266

Gnomad4 NFE AF: 0.265

Gnomad4 OTH AF: 0.248

Alfa AF: 0.261 Hom.: 7387

Bravo AF: 0.216

Asia WGS AF: 0.165 AC: 580 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.30
DANN	Benign	0.67

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

Publications

LitVar

Other links and lift over

dbSNP: rs2036402; hg19: chr5-156464242; COSMIC: COSV59400067;