chr5-157052498-A-G

Variant names:

• chr5-157052498-A-G
• rs1553316
• NM_001173393.3:c.536T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_001173393.3(HAVCR1):​c.536T>C​(p.Leu179Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.857 in 1,613,744 control chromosomes in the GnomAD database, including 594,062 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.87 (57328 hom., cov: 33)
  • Exomes 𝑓: 0.86 (536734 hom.)
• Consequence: HAVCR1 NM_001173393.3 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -1.35
• Publications: 36 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.1887994E-6).
• BP6: Variant 5-157052498-A-G is Benign according to our data. Variant chr5-157052498-A-G is described in ClinVar as Benign. ClinVar VariationId is 3059144.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.965 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001173393.3. 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.536T>C	p.Leu179Pro	missense	Exon 4 of 9	NP_001166864.1
	HAVCR1	NM_001308156.2		c.536T>C	p.Leu179Pro	missense	Exon 4 of 8	NP_001295085.1
	HAVCR1	NM_012206.3		c.536T>C	p.Leu179Pro	missense	Exon 3 of 8	NP_036338.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HAVCR1	ENST00000523175.6	TSL:1 MANE Select	c.536T>C	p.Leu179Pro	missense	Exon 4 of 9	ENSP00000427898.1
	HAVCR1	ENST00000339252.8	TSL:1	c.536T>C	p.Leu179Pro	missense	Exon 3 of 8	ENSP00000344844.3
	HAVCR1	ENST00000522693.5	TSL:2	c.536T>C	p.Leu179Pro	missense	Exon 4 of 8	ENSP00000428524.1

Frequencies

GnomAD3 genomes AF: 0.868 AC: 131782 AN: 151798 Hom.: 57277 Cov.: 33

Gnomad AFR AF: 0.875

Gnomad AMI AF: 0.982

Gnomad AMR AF: 0.911

Gnomad ASJ AF: 0.907

Gnomad EAS AF: 0.987

Gnomad SAS AF: 0.950

Gnomad FIN AF: 0.856

Gnomad MID AF: 0.870

Gnomad NFE AF: 0.838

Gnomad OTH AF: 0.874

GnomAD2 exomes AF: 0.884 AC: 220772 AN: 249610 AF XY: 0.886

Gnomad AFR exome AF: 0.880

Gnomad AMR exome AF: 0.936

Gnomad ASJ exome AF: 0.902

Gnomad EAS exome AF: 0.990

Gnomad FIN exome AF: 0.846

Gnomad NFE exome AF: 0.840

Gnomad OTH exome AF: 0.869

GnomAD4 exome AF: 0.856 AC: 1251008 AN: 1461828 Hom.: 536734 Cov.: 63 AF XY: 0.858 AC XY: 624291 AN XY: 727208

African (AFR) AF: 0.878 AC: 29381 AN: 33480

American (AMR) AF: 0.932 AC: 41677 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.904 AC: 23623 AN: 26136

East Asian (EAS) AF: 0.982 AC: 38977 AN: 39700

South Asian (SAS) AF: 0.954 AC: 82294 AN: 86258

European-Finnish (FIN) AF: 0.846 AC: 45174 AN: 53418

Middle Eastern (MID) AF: 0.877 AC: 5059 AN: 5768

European-Non Finnish (NFE) AF: 0.839 AC: 932599 AN: 1111950

Other (OTH) AF: 0.865 AC: 52224 AN: 60396

GnomAD4 genome AF: 0.868 AC: 131890 AN: 151916 Hom.: 57328 Cov.: 33 AF XY: 0.872 AC XY: 64738 AN XY: 74264

African (AFR) AF: 0.875 AC: 36261 AN: 41434

American (AMR) AF: 0.911 AC: 13908 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.907 AC: 3143 AN: 3464

East Asian (EAS) AF: 0.987 AC: 5091 AN: 5156

South Asian (SAS) AF: 0.950 AC: 4574 AN: 4816

European-Finnish (FIN) AF: 0.856 AC: 9046 AN: 10564

Middle Eastern (MID) AF: 0.874 AC: 257 AN: 294

European-Non Finnish (NFE) AF: 0.838 AC: 56876 AN: 67902

Other (OTH) AF: 0.874 AC: 1842 AN: 2108

Alfa AF: 0.853 Hom.: 183121

Bravo AF: 0.873

TwinsUK AF: 0.845 AC: 3135

ALSPAC AF: 0.840 AC: 3239

ESP6500AA AF: 0.881 AC: 3746

ESP6500EA AF: 0.840 AC: 7110

ExAC AF: 0.884 AC: 107012

Asia WGS AF: 0.957 AC: 3330 AN: 3478

EpiCase AF: 0.847

EpiControl AF: 0.845

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

HAVCR1-related disorder Benign:1

Oct 17, 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 v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.044
BayesDel_addAF	Benign	-0.84	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.14
DANN	Benign	0.077
DEOGEN2	Benign	0.0069	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.00048	N
LIST_S2	Benign	0.25	T
MetaRNN	Benign	0.0000012	T
MetaSVM	Benign	-1.1	T
PhyloP100		-1.4
PrimateAI	Benign	0.20	T
PROVEAN	Benign	2.5	N
REVEL	Benign	0.017
Sift	Benign	0.25	T
Sift4G	Benign	0.23	T
Polyphen		0.0	B
Vest4		0.022
MPC		0.31
ClinPred		0.0022	T
GERP RS		-2.3
gMVP		0.080
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: rs1553316; hg19: chr5-156479509; COSMIC: COSV59402931; COSMIC: COSV59402931;