rs9859136

Positions:

• chr3-46053778-G-A

Variant summary

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

The NM_001381860.1(XCR1):​c.-32+142C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 151,944 control chromosomes in the GnomAD database, including 2,415 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 0.12 (2415 hom., cov: 31)
• Consequence: XCR1 NM_001381860.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.04

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.328 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XCR1	NM_001381860.1	c.-32+142C>T		intron_variant			NP_001368789.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XCR1	ENST00000683768.1	c.-32+142C>T		intron_variant				ENSP00000507745.1

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17757 AN: 151826 Hom.: 2410 Cov.: 31

Gnomad AFR AF: 0.333

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0505

Gnomad ASJ AF: 0.00808

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00884

Gnomad FIN AF: 0.0439

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0366

Gnomad OTH AF: 0.0817

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

GnomAD4 genome AF: 0.117 AC: 17785 AN: 151944 Hom.: 2415 Cov.: 31 AF XY: 0.112 AC XY: 8347 AN XY: 74268

Gnomad4 AFR AF: 0.333

Gnomad4 AMR AF: 0.0504

Gnomad4 ASJ AF: 0.00808

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00885

Gnomad4 FIN AF: 0.0439

Gnomad4 NFE AF: 0.0366

Gnomad4 OTH AF: 0.0808

Alfa AF: 0.0866 Hom.: 200

Bravo AF: 0.130

Asia WGS AF: 0.0250 AC: 89 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.95
DANN	Benign	0.18

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9859136; hg19: chr3-46095270;