rs17215981

chr3-46082926-A-Gchr3-46082926-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000682415.1(ENSG00000288703):n.76-7512A>G variant causes a intron, non coding transcript 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: ENST00000682415.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.587

Genes affected

(HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XCR1	NM_001381860.1	c.-263+2868T>C		intron_variant
XCR1	NR_170111.1	n.51+2868T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000682415.1	n.76-7512A>G		intron_variant, non_coding_transcript_variant
XCR1	ENST00000683768.1	c.-515+2868T>C		intron_variant				P1

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

Gnomad4 AFR AF: 0.0181

Gnomad4 AMR AF: 0.0665

Gnomad4 ASJ AF: 0.182

Gnomad4 EAS AF: 0.0434

Gnomad4 SAS AF: 0.338

Gnomad4 FIN AF: 0.145

Gnomad4 NFE AF: 0.110

Gnomad4 OTH AF: 0.0941

Alfa AF: 0.0713 Hom.: 115

Bravo AF: 0.0743

Asia WGS AF: 0.191 AC: 665 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	3.4
Dann	Benign	0.74

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs17215981; hg19: chr3-46124418;