rs115924839

Variant names:

• chr5-157052453-G-A
• rs115924839
• NM_001173393.3:c.581C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-157052453-G-A
• chr5-157052453-G-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001173393.3(HAVCR1):​c.581C>T​(p.Thr194Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00244 in 1,603,852 control chromosomes in the GnomAD database, including 87 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.013 (47 hom., cov: 35)
  • Exomes 𝑓: 0.0013 (40 hom.)
• Consequence: HAVCR1 NM_001173393.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.598
• Publications: 11 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 (MetaRNN=0.002854973).
• BP6: Variant 5-157052453-G-A is Benign according to our data. Variant chr5-157052453-G-A is described in ClinVar as Benign. ClinVar VariationId is 769669.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.013 (1981/152302) while in subpopulation AFR AF = 0.0442 (1836/41556). AF 95% confidence interval is 0.0425. There are 47 homozygotes in GnomAd4. There are 948 alleles in the male GnomAd4 subpopulation. Median coverage is 35. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 47 AR gene

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.581C>T	p.Thr194Met	missense	Exon 4 of 9	NP_001166864.1	Q96D42
	HAVCR1	NM_001308156.2		c.581C>T	p.Thr194Met	missense	Exon 4 of 8	NP_001295085.1	E9PFX0
	HAVCR1	NM_012206.3		c.581C>T	p.Thr194Met	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.581C>T	p.Thr194Met	missense	Exon 4 of 9	ENSP00000427898.1	Q96D42
	HAVCR1	ENST00000339252.8	TSL:1	c.581C>T	p.Thr194Met	missense	Exon 3 of 8	ENSP00000344844.3	Q96D42
	HAVCR1	ENST00000522693.5	TSL:2	c.581C>T	p.Thr194Met	missense	Exon 4 of 8	ENSP00000428524.1	E9PFX0

Frequencies

GnomAD3 genomes AF: 0.0129 AC: 1958 AN: 152184 Hom.: 44 Cov.: 35

Gnomad AFR AF: 0.0438

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00707

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000279

Gnomad OTH AF: 0.00765

GnomAD2 exomes AF: 0.00321 AC: 802 AN: 249600 AF XY: 0.00246

Gnomad AFR exome AF: 0.0442

Gnomad AMR exome AF: 0.00284

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000556

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000971

Gnomad OTH exome AF: 0.000495

GnomAD4 exome AF: 0.00133 AC: 1929 AN: 1451550 Hom.: 40 Cov.: 52 AF XY: 0.00110 AC XY: 795 AN XY: 721790

African (AFR) AF: 0.0448 AC: 1484 AN: 33120

American (AMR) AF: 0.00309 AC: 135 AN: 43718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25758

East Asian (EAS) AF: 0.0000254 AC: 1 AN: 39340

South Asian (SAS) AF: 0.000153 AC: 13 AN: 85014

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53052

Middle Eastern (MID) AF: 0.00227 AC: 13 AN: 5736

European-Non Finnish (NFE) AF: 0.0000805 AC: 89 AN: 1105868

Other (OTH) AF: 0.00324 AC: 194 AN: 59944

GnomAD4 genome AF: 0.0130 AC: 1981 AN: 152302 Hom.: 47 Cov.: 35 AF XY: 0.0127 AC XY: 948 AN XY: 74474

African (AFR) AF: 0.0442 AC: 1836 AN: 41556

American (AMR) AF: 0.00706 AC: 108 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000279 AC: 19 AN: 68020

Other (OTH) AF: 0.00757 AC: 16 AN: 2114

Alfa AF: 0.00493 Hom.: 24

Bravo AF: 0.0153

ESP6500AA AF: 0.0422 AC: 177

ESP6500EA AF: 0.000237 AC: 2

ExAC AF: 0.00391 AC: 473

Asia WGS AF: 0.00375 AC: 13 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.000178

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.76	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.0
DANN	Benign	0.82
DEOGEN2	Benign	0.024	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.049	N
LIST_S2	Benign	0.43	T
MetaRNN	Benign	0.0029	T
MetaSVM	Benign	-0.99	T
PhyloP100		0.60
PrimateAI	Benign	0.20	T
PROVEAN	Benign	-0.93	N
REVEL	Benign	0.028
Sift	Benign	0.58	T
Sift4G	Benign	0.24	T
Polyphen		0.0050	B
Vest4		0.17
MVP		0.061
MPC		0.20
ClinPred		0.00099	T
GERP RS		-0.54
gMVP		0.23
Mutation Taster		=100/0	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: rs115924839; hg19: chr5-156479464;