Genetic Variant HAVCR1:c.-422G>T (chr5-157058365-C-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000339252.8(HAVCR1):c.-422G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0069 in 158,408 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0069 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0059 ( 1 hom. )

Consequence

HAVCR1
ENST00000339252.8 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.461

Publications

0 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: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000339252.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
HAVCR1	NM_001173393.3	MANE Select	c.-12-410G>T	intron	N/A	NP_001166864.1
HAVCR1	NM_001308156.2		c.-133-289G>T	intron	N/A	NP_001295085.1
HAVCR1	NM_012206.3		c.-422G>T	upstream_gene	N/A	NP_036338.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
HAVCR1	ENST00000339252.8	TSL:1	c.-422G>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 8	ENSP00000344844.3
HAVCR1	ENST00000339252.8	TSL:1	c.-422G>T	5_prime_UTR	Exon 1 of 8	ENSP00000344844.3
HAVCR1	ENST00000523175.6	TSL:1 MANE Select	c.-12-410G>T	intron	N/A	ENSP00000427898.1

Frequencies

GnomAD3 genomes

AF:

0.00693

AC:

1054

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00224

Gnomad AMI

AF:

0.0462

Gnomad AMR

AF:

0.00583

Gnomad ASJ

AF:

0.00519

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00405

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0111

Gnomad OTH

AF:

0.00335

GnomAD4 exome

AF:

0.00587

AC:

AN:

6128

Hom.:

Cov.:

AF XY:

0.00483

AC XY:

AN XY:

3310

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

140

American (AMR)

AF:

0.00345

AC:

AN:

580

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

112

East Asian (EAS)

AF:

0.00

AC:

AN:

254

South Asian (SAS)

AF:

0.00

AC:

AN:

500

European-Finnish (FIN)

AF:

0.00455

AC:

AN:

220

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00733

AC:

AN:

3958

Other (OTH)

AF:

0.0114

AC:

AN:

352

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00694

AC:

1057

AN:

152280

Hom.:

Cov.:

AF XY:

0.00619

AC XY:

461

AN XY:

74450

show subpopulations

African (AFR)

AF:

0.00224

AC:

AN:

41572

American (AMR)

AF:

0.00575

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00519

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5182

South Asian (SAS)

AF:

0.00124

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00405

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0111

AC:

755

AN:

68012

Other (OTH)

AF:

0.00520

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

111

167

222

278

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00460

Hom.:

Bravo

AF:

0.00675

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

2.4

(source)

DANN

Benign

0.85

PhyloP100

-0.46

PromoterAI

0.048

Neutral

(source)

Mutation Taster

=300/0

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over