5-157029720-G-T

Variant names:

• chr5-157029720-G-T
• rs111759551
• NM_001173393.3:c.*13C>A

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP6 BS1 BS2

The NM_001308156.2(HAVCR1):​c.1074C>A​(p.Cys358*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00166 in 1,612,780 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0083 (18 hom., cov: 31)
  • Exomes 𝑓: 0.00096 (18 hom.)
• Consequence: HAVCR1 NM_001308156.2 stop_gained
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.0320
• Publications: 7 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 -9 ACMG points.

• BP6: Variant 5-157029720-G-T is Benign according to our data. Variant chr5-157029720-G-T is described in ClinVar as Benign. ClinVar VariationId is 3037347.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00831 (1264/152042) while in subpopulation AFR AF = 0.028 (1162/41480). AF 95% confidence interval is 0.0267. There are 18 homozygotes in GnomAd4. There are 597 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 18 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001308156.2. 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.*13C>A		3_prime_UTR	Exon 9 of 9	NP_001166864.1	Q96D42
	HAVCR1	NM_001308156.2		c.1074C>A	p.Cys358*	stop_gained	Exon 8 of 8	NP_001295085.1	E9PFX0
	HAVCR1	NM_012206.3		c.*13C>A		3_prime_UTR	Exon 8 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.*13C>A		3_prime_UTR	Exon 9 of 9	ENSP00000427898.1	Q96D42
	HAVCR1	ENST00000339252.8	TSL:1	c.*13C>A		3_prime_UTR	Exon 8 of 8	ENSP00000344844.3	Q96D42
	HAVCR1	ENST00000522693.5	TSL:2	c.1074C>A	p.Cys358*	stop_gained	Exon 8 of 8	ENSP00000428524.1	E9PFX0

Frequencies

GnomAD3 genomes AF: 0.00827 AC: 1257 AN: 151926 Hom.: 18 Cov.: 31

Gnomad AFR AF: 0.0279

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00480

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.00623

GnomAD2 exomes AF: 0.00215 AC: 534 AN: 248422 AF XY: 0.00167

Gnomad AFR exome AF: 0.0267

Gnomad AMR exome AF: 0.00217

Gnomad ASJ exome AF: 0.000199

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000194

Gnomad OTH exome AF: 0.00331

GnomAD4 exome AF: 0.000964 AC: 1408 AN: 1460738 Hom.: 18 Cov.: 30 AF XY: 0.000911 AC XY: 662 AN XY: 726740

African (AFR) AF: 0.0286 AC: 957 AN: 33466

American (AMR) AF: 0.00228 AC: 102 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.000186 AC: 16 AN: 86244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52464

Middle Eastern (MID) AF: 0.00728 AC: 42 AN: 5768

European-Non Finnish (NFE) AF: 0.0000944 AC: 105 AN: 1111884

Other (OTH) AF: 0.00306 AC: 185 AN: 60386

GnomAD4 genome AF: 0.00831 AC: 1264 AN: 152042 Hom.: 18 Cov.: 31 AF XY: 0.00804 AC XY: 597 AN XY: 74296

African (AFR) AF: 0.0280 AC: 1162 AN: 41480

American (AMR) AF: 0.00479 AC: 73 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5156

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10562

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 68000

Other (OTH) AF: 0.00616 AC: 13 AN: 2110

Alfa AF: 0.00434 Hom.: 1

Bravo AF: 0.00968

ESP6500AA AF: 0.0295 AC: 111

ESP6500EA AF: 0.000364 AC: 3

ExAC AF: 0.00258 AC: 312

Asia WGS AF: 0.00375 AC: 13 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

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_addAF	Benign	-0.74	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.3
DANN	Benign	0.97
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.043	N
PhyloP100		-0.032
Vest4		0.60
GERP RS		-1.2
Mutation Taster		=195/5	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: rs111759551; hg19: chr5-156456731;