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.

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	Effect	Exon Rank	Protein	UniProt
HAVCR1	NM_001173393.3	MANE Select	c.673+49C>G	intron	N/A	NP_001166864.1	Q96D42
HAVCR1	NM_001308156.2		c.673+49C>G	intron	N/A	NP_001295085.1	E9PFX0
HAVCR1	NM_012206.3		c.673+49C>G	intron	N/A	NP_036338.2	B4DPB1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HAVCR1	ENST00000523175.6	TSL:1 MANE Select	c.673+49C>G	intron	N/A	ENSP00000427898.1	Q96D42
HAVCR1	ENST00000339252.8	TSL:1	c.673+49C>G	intron	N/A	ENSP00000344844.3	Q96D42
HAVCR1	ENST00000522693.5	TSL:2	c.673+49C>G	intron	N/A	ENSP00000428524.1	E9PFX0

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over