chr5-157052498-A-T

Variant names:

• chr5-157052498-A-T
• rs1553316
• NM_001173393.3:c.536T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001173393.3(HAVCR1):​c.536T>A​(p.Leu179Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L179P) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: HAVCR1 NM_001173393.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35
• Publications: 36 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.049358785).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HAVCR1	NM_001173393.3	MANE Select	c.536T>A	p.Leu179Gln	missense	Exon 4 of 9	NP_001166864.1
	HAVCR1	NM_001308156.2		c.536T>A	p.Leu179Gln	missense	Exon 4 of 8	NP_001295085.1
	HAVCR1	NM_012206.3		c.536T>A	p.Leu179Gln	missense	Exon 3 of 8	NP_036338.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HAVCR1	ENST00000523175.6	TSL:1 MANE Select	c.536T>A	p.Leu179Gln	missense	Exon 4 of 9	ENSP00000427898.1
	HAVCR1	ENST00000339252.8	TSL:1	c.536T>A	p.Leu179Gln	missense	Exon 3 of 8	ENSP00000344844.3
	HAVCR1	ENST00000522693.5	TSL:2	c.536T>A	p.Leu179Gln	missense	Exon 4 of 8	ENSP00000428524.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 63

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.097
DANN	Benign	0.14
DEOGEN2	Benign	0.010	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.00090	T
MetaRNN	Benign	0.049	T
MetaSVM	Benign	-0.98	T
PhyloP100		-1.4
PrimateAI	Benign	0.19	T
PROVEAN	Benign	0.41	N
REVEL	Benign	0.014
Sift	Benign	0.37	T
Sift4G	Benign	0.17	T
Polyphen		0.026	B
Vest4		0.10
MutPred		0.25		Loss of sheet (P = 0.0817)
MVP		0.10
MPC		0.20
ClinPred		0.028	T
GERP RS		-2.3
gMVP		0.12
Mutation Taster		=98/2	polymorphism

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: rs1553316; hg19: chr5-156479509;