rs926658384

Variant names:

• chr4-76035929-T-G
• rs926658384
• NM_005409.5:c.59A>C

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_005409.5(CXCL11):​c.59A>C​(p.Gln20Pro) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000868 in 1,612,982 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000066 (0 hom., cov: 34)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: CXCL11 NM_005409.5 missense, splice_region
• Scores: Splicing: ADA: 0.00007554
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.13
• Publications: 1 publications found

Genes affected

CXCL11 (HGNC:10638): (C-X-C motif chemokine ligand 11) Chemokines are a group of small (approximately 8 to 14 kD), mostly basic, structurally related molecules that regulate cell trafficking of various types of leukocytes through interactions with a subset of 7-transmembrane, G protein-coupled receptors. Chemokines also play fundamental roles in the development, homeostasis, and function of the immune system, and they have effects on cells of the central nervous system as well as on endothelial cells involved in angiogenesis or angiostasis. Chemokines are divided into 2 major subfamilies, CXC and CC. This antimicrobial gene is a CXC member of the chemokine superfamily. Its encoded protein induces a chemotactic response in activated T-cells and is the dominant ligand for CXC receptor-3. The gene encoding this protein contains 4 exons and at least three polyadenylation signals which might reflect cell-specific regulation of expression. IFN-gamma is a potent inducer of transcription of this gene. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2014]

ART3 (HGNC:725): (ADP-ribosyltransferase 3 (inactive)) This gene encodes an arginine-specific ADP-ribosyltransferase. The encoded protein catalyzes a reversible reaction which modifies proteins by the addition or removal of ADP-ribose to an arginine residue to regulate the function of the modified protein. An ADP-ribosyltransferase pseudogene is located on chromosome 11. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.29550904).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005409.5. 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
	CXCL11	NM_005409.5	MANE Select	c.59A>C	p.Gln20Pro	missense splice_region	Exon 1 of 4	NP_005400.1	O14625
	CXCL11	NM_001302123.2		c.59A>C	p.Gln20Pro	missense splice_region	Exon 1 of 4	NP_001289052.1
	ART3	NM_001130017.3		c.-10+24609T>G		intron	N/A	NP_001123489.1	Q13508-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CXCL11	ENST00000306621.8	TSL:1 MANE Select	c.59A>C	p.Gln20Pro	missense splice_region	Exon 1 of 4	ENSP00000306884.3	O14625
	ART3	ENST00000341029.9	TSL:1	c.-10+24609T>G		intron	N/A	ENSP00000343843.5	Q13508-2
	ART3	ENST00000513122.5	TSL:1	c.-124-22061T>G		intron	N/A	ENSP00000422287.1	E7ESB3

Frequencies

GnomAD3 genomes AF: 0.0000657 AC: 10 AN: 152262 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1460720 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726642

African (AFR) AF: 0.00 AC: 0 AN: 33442

American (AMR) AF: 0.0000449 AC: 2 AN: 44516

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26110

East Asian (EAS) AF: 0.00 AC: 0 AN: 39644

South Asian (SAS) AF: 0.00 AC: 0 AN: 85966

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111536

Other (OTH) AF: 0.0000331 AC: 2 AN: 60336

GnomAD4 genome AF: 0.0000657 AC: 10 AN: 152262 Hom.: 0 Cov.: 34 AF XY: 0.0000538 AC XY: 4 AN XY: 74392

African (AFR) AF: 0.00 AC: 0 AN: 41474

American (AMR) AF: 0.000654 AC: 10 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5208

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000159

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.096	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	19
DANN	Benign	0.89
DEOGEN2	Uncertain	0.47	T
Eigen	Benign	0.025
Eigen_PC	Benign	-0.055
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-1.0	T
PhyloP100		2.1
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-4.1	D
REVEL	Benign	0.15
Sift	Benign	0.13	T
Sift4G	Benign	0.19	T
Polyphen		0.015	B
Vest4		0.41
MutPred		0.47		Gain of relative solvent accessibility (P = 0.1684)
MVP		0.67
MPC		0.10
ClinPred		0.46	T
GERP RS		3.2
PromoterAI		-0.013	Neutral
Varity_R		0.45
gMVP		0.61
Mutation Taster		=82/18	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000076
dbscSNV1_RF	Benign	0.020
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: rs926658384; hg19: chr4-76957082;