rs6817952

Variant names:

• chr4-76035890-G-A
• rs6817952
• NM_005409.5:c.61+37C>T

Your query was ambiguous. Multiple possible variants found:

• chr4-76035890-G-A
• chr4-76035890-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005409.5(CXCL11):​c.61+37C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 1,562,256 control chromosomes in the GnomAD database, including 19,468 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 0.13 (1684 hom., cov: 33)
  • Exomes 𝑓: 0.15 (17784 hom.)
• Consequence: CXCL11 NM_005409.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.140
• Publications: 8 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CXCL11	NM_005409.5	c.61+37C>T		intron_variant	Intron 1 of 3	ENST00000306621.8	NP_005400.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CXCL11	ENST00000306621.8	c.61+37C>T		intron_variant	Intron 1 of 3	1	NM_005409.5	ENSP00000306884.3

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19708 AN: 152082 Hom.: 1682 Cov.: 33

Gnomad AFR AF: 0.0564

Gnomad AMI AF: 0.248

Gnomad AMR AF: 0.151

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.386

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.106

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.123

GnomAD2 exomes AF: 0.155 AC: 36418 AN: 234948 AF XY: 0.153

Gnomad AFR exome AF: 0.0536

Gnomad AMR exome AF: 0.169

Gnomad ASJ exome AF: 0.183

Gnomad EAS exome AF: 0.393

Gnomad FIN exome AF: 0.0988

Gnomad NFE exome AF: 0.149

Gnomad OTH exome AF: 0.154

GnomAD4 exome AF: 0.151 AC: 213112 AN: 1410056 Hom.: 17784 Cov.: 22 AF XY: 0.151 AC XY: 105839 AN XY: 703170

African (AFR) AF: 0.0498 AC: 1579 AN: 31732

American (AMR) AF: 0.165 AC: 6689 AN: 40538

Ashkenazi Jewish (ASJ) AF: 0.185 AC: 4656 AN: 25180

East Asian (EAS) AF: 0.375 AC: 14768 AN: 39356

South Asian (SAS) AF: 0.102 AC: 8342 AN: 81838

European-Finnish (FIN) AF: 0.0995 AC: 5298 AN: 53262

Middle Eastern (MID) AF: 0.106 AC: 596 AN: 5600

European-Non Finnish (NFE) AF: 0.151 AC: 162255 AN: 1073942

Other (OTH) AF: 0.152 AC: 8929 AN: 58608

GnomAD4 genome AF: 0.130 AC: 19715 AN: 152200 Hom.: 1684 Cov.: 33 AF XY: 0.129 AC XY: 9580 AN XY: 74400

African (AFR) AF: 0.0563 AC: 2339 AN: 41552

American (AMR) AF: 0.151 AC: 2307 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.189 AC: 654 AN: 3468

East Asian (EAS) AF: 0.386 AC: 1999 AN: 5182

South Asian (SAS) AF: 0.124 AC: 600 AN: 4822

European-Finnish (FIN) AF: 0.106 AC: 1125 AN: 10586

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.149 AC: 10157 AN: 67994

Other (OTH) AF: 0.125 AC: 264 AN: 2106

Alfa AF: 0.136 Hom.: 312

Bravo AF: 0.131

Asia WGS AF: 0.240 AC: 831 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	9.6
DANN	Benign	0.69
PhyloP100		0.14
PromoterAI		-0.017	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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: rs6817952; hg19: chr4-76957043; COSMIC: COSV60666216; COSMIC: COSV60666216;