chr5-157052413-A-C

Variant names:

• chr5-157052413-A-C
• rs1553317
• NM_001173393.3:c.621T>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_001173393.3(HAVCR1):​c.621T>G​(p.Thr207Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.857 in 1,613,720 control chromosomes in the GnomAD database, including 594,257 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.87 (57539 hom., cov: 34)
  • Exomes 𝑓: 0.86 (536718 hom.)
• Consequence: HAVCR1 NM_001173393.3 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -3.27
• Publications: 23 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BP6: Variant 5-157052413-A-C is Benign according to our data. Variant chr5-157052413-A-C is described in ClinVar as Benign. ClinVar VariationId is 3059346.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-3.27 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.965 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.621T>G	p.Thr207Thr	synonymous	Exon 4 of 9	NP_001166864.1	Q96D42
	HAVCR1	NM_001308156.2		c.621T>G	p.Thr207Thr	synonymous	Exon 4 of 8	NP_001295085.1	E9PFX0
	HAVCR1	NM_012206.3		c.621T>G	p.Thr207Thr	synonymous	Exon 3 of 8	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.621T>G	p.Thr207Thr	synonymous	Exon 4 of 9	ENSP00000427898.1	Q96D42
	HAVCR1	ENST00000339252.8	TSL:1	c.621T>G	p.Thr207Thr	synonymous	Exon 3 of 8	ENSP00000344844.3	Q96D42
	HAVCR1	ENST00000522693.5	TSL:2	c.621T>G	p.Thr207Thr	synonymous	Exon 4 of 8	ENSP00000428524.1	E9PFX0

Frequencies

GnomAD3 genomes AF: 0.869 AC: 132164 AN: 152138 Hom.: 57488 Cov.: 34

Gnomad AFR AF: 0.876

Gnomad AMI AF: 0.984

Gnomad AMR AF: 0.911

Gnomad ASJ AF: 0.908

Gnomad EAS AF: 0.987

Gnomad SAS AF: 0.950

Gnomad FIN AF: 0.857

Gnomad MID AF: 0.870

Gnomad NFE AF: 0.838

Gnomad OTH AF: 0.876

GnomAD2 exomes AF: 0.884 AC: 220762 AN: 249590 AF XY: 0.886

Gnomad AFR exome AF: 0.880

Gnomad AMR exome AF: 0.936

Gnomad ASJ exome AF: 0.902

Gnomad EAS exome AF: 0.989

Gnomad FIN exome AF: 0.846

Gnomad NFE exome AF: 0.840

Gnomad OTH exome AF: 0.869

GnomAD4 exome AF: 0.856 AC: 1250808 AN: 1461464 Hom.: 536718 Cov.: 48 AF XY: 0.859 AC XY: 624204 AN XY: 727046

African (AFR) AF: 0.878 AC: 29377 AN: 33474

American (AMR) AF: 0.932 AC: 41681 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.904 AC: 23622 AN: 26132

East Asian (EAS) AF: 0.982 AC: 38972 AN: 39696

South Asian (SAS) AF: 0.954 AC: 82294 AN: 86256

European-Finnish (FIN) AF: 0.846 AC: 45175 AN: 53420

Middle Eastern (MID) AF: 0.877 AC: 5059 AN: 5768

European-Non Finnish (NFE) AF: 0.839 AC: 932415 AN: 1111616

Other (OTH) AF: 0.865 AC: 52213 AN: 60378

GnomAD4 genome AF: 0.869 AC: 132272 AN: 152256 Hom.: 57539 Cov.: 34 AF XY: 0.872 AC XY: 64945 AN XY: 74436

African (AFR) AF: 0.876 AC: 36377 AN: 41540

American (AMR) AF: 0.912 AC: 13939 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.908 AC: 3152 AN: 3472

East Asian (EAS) AF: 0.987 AC: 5119 AN: 5184

South Asian (SAS) AF: 0.950 AC: 4590 AN: 4830

European-Finnish (FIN) AF: 0.857 AC: 9086 AN: 10602

Middle Eastern (MID) AF: 0.874 AC: 257 AN: 294

European-Non Finnish (NFE) AF: 0.838 AC: 57006 AN: 68018

Other (OTH) AF: 0.875 AC: 1849 AN: 2112

Alfa AF: 0.852 Hom.: 83476

Bravo AF: 0.873

EpiCase AF: 0.847

EpiControl AF: 0.845

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	HAVCR1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.28
DANN	Benign	0.34
PhyloP100		-3.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs1553317; hg19: chr5-156479424; COSMIC: COSV108176032; COSMIC: COSV108176032;