Genetic Variant HAVCR1:c.-416G>C (chr5-157058359-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000339252.8(HAVCR1):c.-416G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.508 in 158,890 control chromosomes in the GnomAD database, including 20,747 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 0.51 ( 19725 hom., cov: 32)

Exomes 𝑓: 0.53 ( 1022 hom. )

Consequence

HAVCR1
ENST00000339252.8 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.272

Publications

17 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.632 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HAVCR1	NM_001173393.3 link	c.-12-404G>C		intron_variant	Intron 1 of 8	ENST00000523175.6	NP_001166864.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HAVCR1	ENST00000523175.6 link	c.-12-404G>C		intron_variant	Intron 1 of 8	1	NM_001173393.3	ENSP00000427898.1

Frequencies

GnomAD3 genomes

AF:

0.507

AC:

76947

AN:

151866

Hom.:

19710

Cov.:

show subpopulations

Gnomad AFR

AF:

0.426

Gnomad AMI

AF:

0.767

Gnomad AMR

AF:

0.515

Gnomad ASJ

AF:

0.611

Gnomad EAS

AF:

0.651

Gnomad SAS

AF:

0.627

Gnomad FIN

AF:

0.466

Gnomad MID

AF:

0.519

Gnomad NFE

AF:

0.531

Gnomad OTH

AF:

0.522

GnomAD4 exome

AF:

0.535

AC:

3693

AN:

6906

Hom.:

1022

Cov.:

AF XY:

0.531

AC XY:

1930

AN XY:

3634

show subpopulations

African (AFR)

AF:

0.418

AC:

AN:

158

American (AMR)

AF:

0.435

AC:

269

AN:

618

Ashkenazi Jewish (ASJ)

AF:

0.671

AC:

102

AN:

152

East Asian (EAS)

AF:

0.715

AC:

203

AN:

284

South Asian (SAS)

AF:

0.607

AC:

352

AN:

580

European-Finnish (FIN)

AF:

0.500

AC:

124

AN:

248

Middle Eastern (MID)

AF:

0.556

AC:

AN:

European-Non Finnish (NFE)

AF:

0.532

AC:

2368

AN:

4452

Other (OTH)

AF:

0.503

AC:

199

AN:

396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

160

240

320

400

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

<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:

0.507

AC:

77005

AN:

151984

Hom.:

19725

Cov.:

AF XY:

0.507

AC XY:

37678

AN XY:

74272

show subpopulations

African (AFR)

AF:

0.426

AC:

17683

AN:

41462

American (AMR)

AF:

0.515

AC:

7852

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.611

AC:

2121

AN:

3472

East Asian (EAS)

AF:

0.650

AC:

3360

AN:

5166

South Asian (SAS)

AF:

0.626

AC:

3015

AN:

4818

European-Finnish (FIN)

AF:

0.466

AC:

4904

AN:

10526

Middle Eastern (MID)

AF:

0.514

AC:

151

AN:

294

European-Non Finnish (NFE)

AF:

0.531

AC:

36109

AN:

67966

Other (OTH)

AF:

0.527

AC:

1114

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1976

3952

5929

7905

9881

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

694

1388

2082

2776

3470

<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:

0.374

Hom.:

959

Bravo

AF:

0.501

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

1.8

(source)

DANN

Benign

0.81

PhyloP100

-0.27

PromoterAI

-0.0096

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over