5-157029698-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001173393.3(HAVCR1):c.*35G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00233 in 1,612,248 control chromosomes in the GnomAD database, including 87 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.013 (47 hom., cov: 31)
  • Exomes 𝑓: 0.0012 (40 hom.)
• Consequence: HAVCR1 NM_001173393.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.143

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0022322536).
• BP6: Variant 5-157029698-C-T is Benign according to our data. Variant chr5-157029698-C-T is described in ClinVar as [Benign]. Clinvar id is 3038946.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0129 (1958/152132) while in subpopulation AFR AF= 0.0452 (1878/41506). AF 95% confidence interval is 0.0435. There are 47 homozygotes in gnomad4. There are 879 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 47 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HAVCR1	NM_001173393.3	c.*35G>A		3_prime_UTR_variant	9/9	ENST00000523175.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HAVCR1	ENST00000523175.6	c.*35G>A		3_prime_UTR_variant	9/9	1	NM_001173393.3	P2
HAVCR1	ENST00000339252.8	c.*35G>A		3_prime_UTR_variant	8/8	1		P2
HAVCR1	ENST00000522693.5	c.1096G>A	p.Glu366Lys	missense_variant	8/8	2		A2

Frequencies

GnomAD3 genomes AF: 0.0129 AC: 1958 AN: 152012 Hom.: 47 Cov.: 31

Gnomad AFR AF: 0.0454

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00348

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00956

GnomAD3 exomes AF: 0.00322 AC: 797 AN: 247664 Hom.: 15 AF XY: 0.00247 AC XY: 332 AN XY: 134566

Gnomad AFR exome AF: 0.0461

Gnomad AMR exome AF: 0.00180

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000655

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000115

Gnomad OTH exome AF: 0.00149

GnomAD4 exome AF: 0.00124 AC: 1804 AN: 1460116 Hom.: 40 Cov.: 30 AF XY: 0.00105 AC XY: 761 AN XY: 726466

Gnomad4 AFR exome AF: 0.0447

Gnomad4 AMR exome AF: 0.00228

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000580

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000360

Gnomad4 OTH exome AF: 0.00257

GnomAD4 genome AF: 0.0129 AC: 1958 AN: 152132 Hom.: 47 Cov.: 31 AF XY: 0.0118 AC XY: 879 AN XY: 74356

Gnomad4 AFR AF: 0.0452

Gnomad4 AMR AF: 0.00341

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000103

Gnomad4 OTH AF: 0.00946

Alfa AF: 0.00765 Hom.: 6

Bravo AF: 0.0146

ESP6500AA AF: 0.0464 AC: 176

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00395 AC: 477

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

HAVCR1-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 11, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.76
Cadd	Benign	10
Dann	Uncertain	0.98
DEOGEN2	Benign	0.090	T;T
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.034	N
MetaRNN	Benign	0.0022	T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N;N;N;N;N
PROVEAN	Benign	-0.94	N;.
REVEL	Benign	0.066
Sift	Uncertain	0.016	D;.
Sift4G	Benign	0.073	T;T
Polyphen		0.0090	B;B
Vest4		0.20
MVP		0.35
ClinPred		0.0014	T
GERP RS		1.7
gMVP		0.16

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: rs145237072; hg19: chr5-156456709;