5-157032845-C-T

Variant names:

• chr5-157032845-C-T
• rs34670839
• NM_001173393.3:c.986+9G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_001173393.3(HAVCR1):​c.986+9G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 1,492,182 control chromosomes in the GnomAD database, including 47,674 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.21 (4110 hom., cov: 32)
  • Exomes 𝑓: 0.25 (43564 hom.)
• Consequence: HAVCR1 NM_001173393.3 intron
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.112
• Publications: 10 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 5-157032845-C-T is Benign according to our data. Variant chr5-157032845-C-T is described in ClinVar as Benign. ClinVar VariationId is 3059623.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.313 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.986+9G>A		intron	N/A	NP_001166864.1	Q96D42
	HAVCR1	NM_001308156.2		c.953-3004G>A		intron	N/A	NP_001295085.1	E9PFX0
	HAVCR1	NM_012206.3		c.986+9G>A		intron	N/A	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.986+9G>A		intron	N/A	ENSP00000427898.1	Q96D42
	HAVCR1	ENST00000339252.8	TSL:1	c.986+9G>A		intron	N/A	ENSP00000344844.3	Q96D42
	HAVCR1	ENST00000522693.5	TSL:2	c.953-3004G>A		intron	N/A	ENSP00000428524.1	E9PFX0

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32266 AN: 151950 Hom.: 4109 Cov.: 32

Gnomad AFR AF: 0.0740

Gnomad AMI AF: 0.281

Gnomad AMR AF: 0.320

Gnomad ASJ AF: 0.272

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.266

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.266

Gnomad OTH AF: 0.250

GnomAD2 exomes AF: 0.250 AC: 60157 AN: 241026 AF XY: 0.247

Gnomad AFR exome AF: 0.0699

Gnomad AMR exome AF: 0.401

Gnomad ASJ exome AF: 0.266

Gnomad EAS exome AF: 0.128

Gnomad FIN exome AF: 0.251

Gnomad NFE exome AF: 0.261

Gnomad OTH exome AF: 0.266

GnomAD4 exome AF: 0.248 AC: 332752 AN: 1340114 Hom.: 43564 Cov.: 21 AF XY: 0.248 AC XY: 166682 AN XY: 673224

African (AFR) AF: 0.0644 AC: 2009 AN: 31204

American (AMR) AF: 0.392 AC: 16300 AN: 41612

Ashkenazi Jewish (ASJ) AF: 0.265 AC: 6688 AN: 25210

East Asian (EAS) AF: 0.117 AC: 4551 AN: 38924

South Asian (SAS) AF: 0.199 AC: 16368 AN: 82194

European-Finnish (FIN) AF: 0.253 AC: 13454 AN: 53162

Middle Eastern (MID) AF: 0.226 AC: 1249 AN: 5528

European-Non Finnish (NFE) AF: 0.257 AC: 258879 AN: 1006002

Other (OTH) AF: 0.236 AC: 13254 AN: 56278

GnomAD4 genome AF: 0.212 AC: 32264 AN: 152068 Hom.: 4110 Cov.: 32 AF XY: 0.212 AC XY: 15786 AN XY: 74304

African (AFR) AF: 0.0738 AC: 3065 AN: 41504

American (AMR) AF: 0.321 AC: 4902 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.272 AC: 942 AN: 3466

East Asian (EAS) AF: 0.125 AC: 646 AN: 5170

South Asian (SAS) AF: 0.206 AC: 993 AN: 4824

European-Finnish (FIN) AF: 0.266 AC: 2805 AN: 10546

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.266 AC: 18055 AN: 67968

Other (OTH) AF: 0.246 AC: 520 AN: 2112

Alfa AF: 0.247 Hom.: 3471

Bravo AF: 0.214

Asia WGS AF: 0.163 AC: 572 AN: 3478

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_noAF	Benign	-0.91
CADD	Benign	6.3
DANN	Benign	0.51
PhyloP100		0.11
Mutation Taster		=100/0	polymorphism (auto)

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: rs34670839; hg19: chr5-156459856; COSMIC: COSV59402142;