5-157045138-C-A

Variant names:

• chr5-157045138-C-A
• rs6555820
• NM_001173393.3:c.782-2456G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001173393.3(HAVCR1):​c.782-2456G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.496 in 151,730 control chromosomes in the GnomAD database, including 18,885 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 0.50 (18885 hom., cov: 31)
• Consequence: HAVCR1 NM_001173393.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.311
• Publications: 6 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.05).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.538 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HAVCR1	NM_001173393.3	MANE Select	c.782-2456G>T		intron	N/A	NP_001166864.1	Q96D42
	HAVCR1	NM_001308156.2		c.782-2456G>T		intron	N/A	NP_001295085.1	E9PFX0
	HAVCR1	NM_012206.3		c.782-2456G>T		intron	N/A	NP_036338.2	B4DPB1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HAVCR1	ENST00000523175.6	TSL:1 MANE Select	c.782-2456G>T		intron	N/A	ENSP00000427898.1	Q96D42
	HAVCR1	ENST00000339252.8	TSL:1	c.782-2456G>T		intron	N/A	ENSP00000344844.3	Q96D42
	HAVCR1	ENST00000522693.5	TSL:2	c.782-2456G>T		intron	N/A	ENSP00000428524.1	E9PFX0

Frequencies

GnomAD3 genomes AF: 0.496 AC: 75213 AN: 151612 Hom.: 18874 Cov.: 31

Gnomad AFR AF: 0.542

Gnomad AMI AF: 0.501

Gnomad AMR AF: 0.548

Gnomad ASJ AF: 0.547

Gnomad EAS AF: 0.331

Gnomad SAS AF: 0.451

Gnomad FIN AF: 0.435

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.477

Gnomad OTH AF: 0.532

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.496 AC: 75263 AN: 151730 Hom.: 18885 Cov.: 31 AF XY: 0.492 AC XY: 36489 AN XY: 74096

African (AFR) AF: 0.542 AC: 22417 AN: 41358

American (AMR) AF: 0.548 AC: 8358 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.547 AC: 1897 AN: 3466

East Asian (EAS) AF: 0.331 AC: 1704 AN: 5154

South Asian (SAS) AF: 0.451 AC: 2167 AN: 4808

European-Finnish (FIN) AF: 0.435 AC: 4561 AN: 10476

Middle Eastern (MID) AF: 0.667 AC: 196 AN: 294

European-Non Finnish (NFE) AF: 0.477 AC: 32397 AN: 67908

Other (OTH) AF: 0.527 AC: 1110 AN: 2106

Alfa AF: 0.373 Hom.: 1337

Bravo AF: 0.507

Asia WGS AF: 0.415 AC: 1447 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.60
DANN	Benign	0.18
PhyloP100		-0.31
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6555820; hg19: chr5-156472149;