rs751498596

Variant names:

• chr3-46020960-C-A
• rs751498596
• NM_001024644.2:c.988G>T

Your query was ambiguous. Multiple possible variants found:

• chr3-46020960-C-A
• chr3-46020960-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001024644.2(XCR1):​c.988G>T​(p.Ala330Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,546 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A330T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: XCR1 NM_001024644.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.104

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.035399765).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XCR1	NM_001024644.2	c.988G>T	p.Ala330Ser	missense_variant	Exon 2 of 2	ENST00000309285.4	NP_001019815.1
XCR1	NM_001381860.1	c.988G>T	p.Ala330Ser	missense_variant	Exon 4 of 4		NP_001368789.1
XCR1	NM_005283.3	c.988G>T	p.Ala330Ser	missense_variant	Exon 3 of 3		NP_005274.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XCR1	ENST00000309285.4	c.988G>T	p.Ala330Ser	missense_variant	Exon 2 of 2	1	NM_001024644.2	ENSP00000310405.3
XCR1	ENST00000395946.3	c.988G>T	p.Ala330Ser	missense_variant	Exon 3 of 3	1		ENSP00000379277.3
XCR1	ENST00000683768.1	c.988G>T	p.Ala330Ser	missense_variant	Exon 6 of 6			ENSP00000507745.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000409 AC: 1 AN: 244690 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 132436

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000333

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1459546 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 725882

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	10
DANN	Benign	0.93
DEOGEN2	Benign	0.060	T
Eigen	Benign	-0.85
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.090	N
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.035	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.4	L
PrimateAI	Benign	0.28	T
PROVEAN	Benign	0.32	N
REVEL	Benign	0.060
Sift	Benign	0.43	T
Sift4G	Benign	0.61	T
Polyphen		0.30	B
Vest4		0.055
MutPred		0.18		Gain of glycosylation at A330 (P = 0.0075);
MVP		0.32
MPC		0.48
ClinPred		0.074	T
GERP RS		3.8
Varity_R		0.042
gMVP		0.44

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

Publications

LitVar

Other links and lift over

dbSNP: rs751498596; hg19: chr3-46062452;