Genetic Variant HAVCR1:p.Thr194Lys (chr5-157052453-G-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001173393.3(HAVCR1):c.581C>A(p.Thr194Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T194M) has been classified as Benign.

Frequency

Genomes: not found (cov: 35)

Consequence

HAVCR1
NM_001173393.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.598

Publications

11 publications found

Variant links:

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]

HAVCR1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.059959024).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HAVCR1	NM_001173393.3	MANE Select	c.581C>A	p.Thr194Lys	missense	Exon 4 of 9	NP_001166864.1	Q96D42
HAVCR1	NM_001308156.2		c.581C>A	p.Thr194Lys	missense	Exon 4 of 8	NP_001295085.1	E9PFX0
HAVCR1	NM_012206.3		c.581C>A	p.Thr194Lys	missense	Exon 3 of 8	NP_036338.2	B4DPB1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HAVCR1	ENST00000523175.6	TSL:1 MANE Select	c.581C>A	p.Thr194Lys	missense	Exon 4 of 9	ENSP00000427898.1	Q96D42
HAVCR1	ENST00000339252.8	TSL:1	c.581C>A	p.Thr194Lys	missense	Exon 3 of 8	ENSP00000344844.3	Q96D42
HAVCR1	ENST00000522693.5	TSL:2	c.581C>A	p.Thr194Lys	missense	Exon 4 of 8	ENSP00000428524.1	E9PFX0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000401

AC:

AN:

249600

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000556

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.63

CADD

Benign

0.49

(source)

DANN

Benign

0.24

DEOGEN2

Benign

0.029

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.097

LIST_S2

Benign

0.33

M_CAP

Benign

0.0022

MetaRNN

Benign

0.060

MetaSVM

Benign

-0.98

PhyloP100

0.60

PrimateAI

Benign

0.21

PROVEAN

Benign

-1.6

REVEL

Benign

0.027

Sift

Benign

0.47

Sift4G

Benign

0.39

Polyphen

0.14

Vest4

0.29

MutPred

0.34

Gain of methylation at T194 (P = 9e-04)

MVP

0.067

MPC

0.23

ClinPred

0.025

GERP RS

-0.54

gMVP

0.36

Mutation Taster

=99/1

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over