3-46082926-A-G

Variant names:

• chr3-46082926-A-G
• rs17215981
• NM_001381860.1:c.-263+2868T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001381860.1(XCR1):​c.-263+2868T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0902 in 152,204 control chromosomes in the GnomAD database, including 997 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.090 (997 hom., cov: 31)
• Consequence: XCR1 NM_001381860.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.587
• Publications: 7 publications found

Genes affected

XCR1 (HGNC:1625): (X-C motif chemokine receptor 1) The protein encoded by this gene is a chemokine receptor belonging to the G protein-coupled receptor superfamily. The family members are characterized by the presence of 7 transmembrane domains. The encoded protein transduces a signal by increasing the intracellular calcium ion level. The viral macrophage inflammatory protein-II is an antagonist of this receptor and blocks signaling. Some studies have implicated a cluster of genes at 3p21.31, including this gene, as associated with COVID-19 risk. The encoded protein may also play a role in cell proliferation and migration in several types of cancer. [provided by RefSeq, Jan 2023]

ENSG00000288703 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.324 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001381860.1. 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
	XCR1	NM_001381860.1		c.-263+2868T>C		intron	N/A	NP_001368789.1
	XCR1	NR_170111.1		n.51+2868T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XCR1	ENST00000683768.1		c.-515+2868T>C		intron	N/A	ENSP00000507745.1
	ENSG00000288703	ENST00000682415.1		n.76-7512A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0904 AC: 13743 AN: 152084 Hom.: 999 Cov.: 31

Gnomad AFR AF: 0.0182

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.0666

Gnomad ASJ AF: 0.182

Gnomad EAS AF: 0.0435

Gnomad SAS AF: 0.337

Gnomad FIN AF: 0.145

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.0932

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0902 AC: 13732 AN: 152204 Hom.: 997 Cov.: 31 AF XY: 0.0962 AC XY: 7160 AN XY: 74406

African (AFR) AF: 0.0181 AC: 751 AN: 41552

American (AMR) AF: 0.0665 AC: 1017 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.182 AC: 629 AN: 3464

East Asian (EAS) AF: 0.0434 AC: 225 AN: 5186

South Asian (SAS) AF: 0.338 AC: 1627 AN: 4816

European-Finnish (FIN) AF: 0.145 AC: 1533 AN: 10576

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.110 AC: 7496 AN: 67992

Other (OTH) AF: 0.0941 AC: 199 AN: 2114

Alfa AF: 0.0705 Hom.: 116

Bravo AF: 0.0743

Asia WGS AF: 0.191 AC: 665 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.4
DANN	Benign	0.74
PhyloP100		0.59

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs17215981; hg19: chr3-46124418;