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. The variant received -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. 17/22 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
• Publications: 2 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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001024644.2. 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
	XCR1	NM_001024644.2	MANE Select	c.988G>T	p.Ala330Ser	missense	Exon 2 of 2	NP_001019815.1	P46094
	XCR1	NM_001381860.1		c.988G>T	p.Ala330Ser	missense	Exon 4 of 4	NP_001368789.1	P46094
	XCR1	NM_005283.3		c.988G>T	p.Ala330Ser	missense	Exon 3 of 3	NP_005274.1	P46094

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XCR1	ENST00000309285.4	TSL:1 MANE Select	c.988G>T	p.Ala330Ser	missense	Exon 2 of 2	ENSP00000310405.3	P46094
	XCR1	ENST00000395946.3	TSL:1	c.988G>T	p.Ala330Ser	missense	Exon 3 of 3	ENSP00000379277.3	P46094
	XCR1	ENST00000683768.1		c.988G>T	p.Ala330Ser	missense	Exon 6 of 6	ENSP00000507745.1	P46094

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000409 AC: 1 AN: 244690 AF XY: 0.00

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 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

African (AFR) AF: 0.00 AC: 0 AN: 33414

American (AMR) AF: 0.00 AC: 0 AN: 44496

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26016

East Asian (EAS) AF: 0.00 AC: 0 AN: 39590

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 85866

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53202

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1110904

Other (OTH) AF: 0.00 AC: 0 AN: 60300

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		-0.10
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
Mutation Taster		=98/2	polymorphism

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: rs751498596; hg19: chr3-46062452;