5-157029698-C-T

Variant names:

• chr5-157029698-C-T
• rs145237072
• NM_001173393.3:c.*35G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BS1 BS2

The NM_001308156.2(HAVCR1):​c.1096G>A​(p.Glu366Lys) variant causes a missense 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. 11/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.013 (47 hom., cov: 31)
  • Exomes 𝑓: 0.0012 (40 hom.)
• Consequence: HAVCR1 NM_001308156.2 missense
• Clinical Significance: Benign no assertion criteria provided 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

Our verdict: Benign. The variant received -13 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 no_assertion_criteria_provided, 0 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 the male GnomAd4 subpopulation. Median coverage is 31. This position FAILED quality control check.
• BS2: High Homozygotes in GnomAd4 at 47 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HAVCR1	NM_001173393.3	c.*35G>A		3_prime_UTR_variant	Exon 9 of 9	ENST00000523175.6	NP_001166864.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HAVCR1	ENST00000523175	c.*35G>A		3_prime_UTR_variant	Exon 9 of 9	1	NM_001173393.3	ENSP00000427898.1
HAVCR1	ENST00000339252	c.*35G>A		3_prime_UTR_variant	Exon 8 of 8	1		ENSP00000344844.3
HAVCR1	ENST00000522693.5	c.1096G>A	p.Glu366Lys	missense_variant	Exon 8 of 8	2		ENSP00000428524.1

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

GnomAD2 exomes AF: 0.00322 AC: 797 AN: 247664 AF XY: 0.00247

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 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 AC: 1496 AN: 33470

Gnomad4 AMR exome AF: 0.00228 AC: 102 AN: 44688

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 26120

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 39682

Gnomad4 SAS exome AF: 0.0000580 AC: 5 AN: 86210

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 51986

Gnomad4 NFE exome AF: 0.0000360 AC: 40 AN: 1111824

Gnomad4 Remaining exome AF: 0.00257 AC: 155 AN: 60370

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 AC: 0.0452465 AN: 0.0452465

Gnomad4 AMR AF: 0.00341 AC: 0.00340582 AN: 0.00340582

Gnomad4 ASJ AF: 0.00 AC: 0 AN: 0

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.00 AC: 0 AN: 0

Gnomad4 FIN AF: 0.00 AC: 0 AN: 0

Gnomad4 NFE AF: 0.000103 AC: 0.000102917 AN: 0.000102917

Gnomad4 OTH AF: 0.00946 AC: 0.00946074 AN: 0.00946074

Alfa AF: 0.0205 Hom.: 24

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: no assertion criteria provided

Submissions by phenotype

HAVCR1-related disorder Benign:1

Sep 11, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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
LIST_S2	Benign	0.32	.;T
MetaRNN	Benign	0.0022	T;T
MetaSVM	Benign	-1.0	T
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
Mutation Taster		=100/0	polymorphism

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;