5-157052453-G-A

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.581C>T(p.Thr194Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00244 in 1,603,852 control chromosomes in the GnomAD database, including 87 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.013 (47 hom., cov: 35)
  • Exomes 𝑓: 0.0013 (40 hom.)
• Consequence: HAVCR1 NM_001173393.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.598

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=0.002854973).
• BP6: Variant 5-157052453-G-A is Benign according to our data. Variant chr5-157052453-G-A is described in ClinVar as [Benign]. Clinvar id is 769669.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.013 (1981/152302) while in subpopulation AFR AF= 0.0442 (1836/41556). AF 95% confidence interval is 0.0425. There are 47 homozygotes in gnomad4. There are 948 alleles in male gnomad4 subpopulation. Median coverage is 35. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 44 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HAVCR1	NM_001173393.3	c.581C>T	p.Thr194Met	missense_variant	4/9	ENST00000523175.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HAVCR1	ENST00000523175.6	c.581C>T	p.Thr194Met	missense_variant	4/9	1	NM_001173393.3	P2

Frequencies

GnomAD3 genomes AF: 0.0129 AC: 1958 AN: 152184 Hom.: 44 Cov.: 35

Gnomad AFR AF: 0.0438

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00707

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000279

Gnomad OTH AF: 0.00765

GnomAD3 exomes AF: 0.00321 AC: 802 AN: 249600 Hom.: 16 AF XY: 0.00246 AC XY: 333 AN XY: 135406

Gnomad AFR exome AF: 0.0442

Gnomad AMR exome AF: 0.00284

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000556

Gnomad SAS exome AF: 0.000131

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000971

Gnomad OTH exome AF: 0.000495

GnomAD4 exome AF: 0.00133 AC: 1929 AN: 1451550 Hom.: 40 Cov.: 52 AF XY: 0.00110 AC XY: 795 AN XY: 721790

Gnomad4 AFR exome AF: 0.0448

Gnomad4 AMR exome AF: 0.00309

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000254

Gnomad4 SAS exome AF: 0.000153

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000805

Gnomad4 OTH exome AF: 0.00324

GnomAD4 genome AF: 0.0130 AC: 1981 AN: 152302 Hom.: 47 Cov.: 35 AF XY: 0.0127 AC XY: 948 AN XY: 74474

Gnomad4 AFR AF: 0.0442

Gnomad4 AMR AF: 0.00706

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000279

Gnomad4 OTH AF: 0.00757

Alfa AF: 0.00246 Hom.: 9

Bravo AF: 0.0153

ESP6500AA AF: 0.0422 AC: 177

ESP6500EA AF: 0.000237 AC: 2

ExAC AF: 0.00391 AC: 473

Asia WGS AF: 0.00375 AC: 13 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.76	T
BayesDel_noAF	Benign	-0.83
Cadd	Benign	2.0
Dann	Benign	0.82
DEOGEN2	Benign	0.024	T;.;.;T;.
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.049	N
MetaRNN	Benign	0.0029	T;T;T;T;T
MetaSVM	Benign	-0.99	T
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Benign	0.20	T
PROVEAN	Benign	-0.93	N;N;N;.;N
REVEL	Benign	0.028
Sift	Benign	0.58	T;T;T;.;T
Sift4G	Benign	0.24	T;T;T;T;T
Polyphen		0.0050	B;.;.;B;.
Vest4		0.17
MVP		0.061
MPC		0.20
ClinPred		0.00099	T
GERP RS		-0.54
gMVP		0.23

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: rs115924839; hg19: chr5-156479464;