5-157052412-C-A

Variant names:

• chr5-157052412-C-A
• rs752404284
• NM_001173393.3:c.622G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001173393.3(HAVCR1):​c.622G>T​(p.Val208Phe) 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. V208I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 34)
• Consequence: HAVCR1 NM_001173393.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0190
• Publications: 1 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.116083235).

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.622G>T	p.Val208Phe	missense	Exon 4 of 9	NP_001166864.1	Q96D42
	HAVCR1	NM_001308156.2		c.622G>T	p.Val208Phe	missense	Exon 4 of 8	NP_001295085.1	E9PFX0
	HAVCR1	NM_012206.3		c.622G>T	p.Val208Phe	missense	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.622G>T	p.Val208Phe	missense	Exon 4 of 9	ENSP00000427898.1	Q96D42
	HAVCR1	ENST00000339252.8	TSL:1	c.622G>T	p.Val208Phe	missense	Exon 3 of 8	ENSP00000344844.3	Q96D42
	HAVCR1	ENST00000522693.5	TSL:2	c.622G>T	p.Val208Phe	missense	Exon 4 of 8	ENSP00000428524.1	E9PFX0

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD2 exomes AF: 0.00000401 AC: 1 AN: 249588 AF XY: 0.00000739

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000883

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	8.2
DANN	Benign	0.79
DEOGEN2	Benign	0.026	T
Eigen	Benign	-0.97
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.042	N
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.0050	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.019
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.076
Sift	Uncertain	0.0020	D
Sift4G	Benign	0.13	T
Polyphen		0.53	P
Vest4		0.33
MutPred		0.26		Loss of sheet (P = 0.0817)
MVP		0.17
MPC		0.26
ClinPred		0.87	D
GERP RS		0.79
gMVP		0.25
Mutation Taster		=95/5	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: rs752404284; hg19: chr5-156479423;