rs1553318

Positions:

• chr5-157052312-G-A
• chr5-157052312-G-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001173393.3(HAVCR1):​c.673+49C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00925 in 1,544,842 control chromosomes in the GnomAD database, including 92 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 0.0070 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0095 (88 hom.)
• Consequence: HAVCR1 NM_001173393.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.209

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HAVCR1	NM_001173393.3	c.673+49C>T		intron_variant		ENST00000523175.6	NP_001166864.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HAVCR1	ENST00000523175.6	c.673+49C>T		intron_variant		1	NM_001173393.3	ENSP00000427898.1

Frequencies

GnomAD3 genomes AF: 0.00697 AC: 1060 AN: 152018 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.00244

Gnomad AMI AF: 0.0484

Gnomad AMR AF: 0.00590

Gnomad ASJ AF: 0.00547

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.00397

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0110

Gnomad OTH AF: 0.00431

GnomAD3 exomes AF: 0.00621 AC: 1504 AN: 241998 Hom.: 9 AF XY: 0.00622 AC XY: 816 AN XY: 131210

Gnomad AFR exome AF: 0.00208

Gnomad AMR exome AF: 0.00416

Gnomad ASJ exome AF: 0.00215

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000795

Gnomad FIN exome AF: 0.00448

Gnomad NFE exome AF: 0.0106

Gnomad OTH exome AF: 0.00509

GnomAD4 exome AF: 0.00950 AC: 13234 AN: 1392706 Hom.: 88 Cov.: 22 AF XY: 0.00933 AC XY: 6493 AN XY: 695890

Gnomad4 AFR exome AF: 0.00175

Gnomad4 AMR exome AF: 0.00440

Gnomad4 ASJ exome AF: 0.00303

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000790

Gnomad4 FIN exome AF: 0.00486

Gnomad4 NFE exome AF: 0.0115

Gnomad4 OTH exome AF: 0.00765

GnomAD4 genome AF: 0.00696 AC: 1059 AN: 152136 Hom.: 4 Cov.: 32 AF XY: 0.00610 AC XY: 454 AN XY: 74368

Gnomad4 AFR AF: 0.00243

Gnomad4 AMR AF: 0.00583

Gnomad4 ASJ AF: 0.00547

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.00397

Gnomad4 NFE AF: 0.0110

Gnomad4 OTH AF: 0.00427

Alfa AF: 0.00571 Hom.: 3103

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.42
DANN	Benign	0.33

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: rs1553318; hg19: chr5-156479323;