Genetic Variant HAVCR1:c.673+49C>G (chr5-157052312-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001173393.3(HAVCR1):c.673+49C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.64 in 1,542,454 control chromosomes in the GnomAD database, including 320,365 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 0.60 ( 27959 hom., cov: 32)

Exomes 𝑓: 0.64 ( 292406 hom. )

Consequence

HAVCR1
NM_001173393.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.209

Publications

26 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=-0.9).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.793 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HAVCR1	NM_001173393.3 link	c.673+49C>G		intron_variant	Intron 4 of 8	ENST00000523175.6	NP_001166864.1	Q96D42B4DPB1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HAVCR1	ENST00000523175.6 link	c.673+49C>G		intron_variant	Intron 4 of 8	1	NM_001173393.3	ENSP00000427898.1		Q96D42

Frequencies

GnomAD3 genomes

AF:

0.596

AC:

90552

AN:

151950

Hom.:

27935

Cov.:

show subpopulations

Gnomad AFR

AF:

0.433

Gnomad AMI

AF:

0.768

Gnomad AMR

AF:

0.690

Gnomad ASJ

AF:

0.626

Gnomad EAS

AF:

0.813

Gnomad SAS

AF:

0.750

Gnomad FIN

AF:

0.690

Gnomad MID

AF:

0.522

Gnomad NFE

AF:

0.628

Gnomad OTH

AF:

0.611

GnomAD2 exomes

AF:

0.670

AC:

162163

AN:

241998

AF XY:

0.671

show subpopulations

Gnomad AFR exome

AF:

0.433

Gnomad AMR exome

AF:

0.802

Gnomad ASJ exome

AF:

0.617

Gnomad EAS exome

AF:

0.807

Gnomad FIN exome

AF:

0.668

Gnomad NFE exome

AF:

0.629

Gnomad OTH exome

AF:

0.634

GnomAD4 exome

AF:

0.645

AC:

896183

AN:

1390386

Hom.:

292406

Cov.:

AF XY:

0.647

AC XY:

449502

AN XY:

694766

show subpopulations

African (AFR)

AF:

0.421

AC:

13424

AN:

31886

American (AMR)

AF:

0.790

AC:

34979

AN:

44278

Ashkenazi Jewish (ASJ)

AF:

0.618

AC:

15471

AN:

25040

East Asian (EAS)

AF:

0.841

AC:

33122

AN:

39392

South Asian (SAS)

AF:

0.738

AC:

61609

AN:

83474

European-Finnish (FIN)

AF:

0.668

AC:

35429

AN:

53030

Middle Eastern (MID)

AF:

0.544

AC:

3058

AN:

5624

European-Non Finnish (NFE)

AF:

0.631

AC:

662791

AN:

1049842

Other (OTH)

AF:

0.628

AC:

36300

AN:

57820

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

14779

29558

44338

59117

73896

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17478

34956

52434

69912

87390

<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:

0.596

AC:

90622

AN:

152068

Hom.:

27959

Cov.:

AF XY:

0.605

AC XY:

44937

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.433

AC:

17957

AN:

41476

American (AMR)

AF:

0.690

AC:

10542

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.626

AC:

2174

AN:

3472

East Asian (EAS)

AF:

0.814

AC:

4206

AN:

5170

South Asian (SAS)

AF:

0.749

AC:

3617

AN:

4826

European-Finnish (FIN)

AF:

0.690

AC:

7291

AN:

10568

Middle Eastern (MID)

AF:

0.524

AC:

154

AN:

294

European-Non Finnish (NFE)

AF:

0.628

AC:

42692

AN:

67972

Other (OTH)

AF:

0.611

AC:

1290

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1814

3629

5443

7258

9072

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

768

1536

2304

3072

3840

<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:

0.549

Hom.:

3103

Bravo

AF:

0.595

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.29

(source)

DANN

Benign

0.34

PhyloP100

-0.21

Mutation Taster

=100/0

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