rs2237061

Variant names:

• chr5-135576640-C-T
• rs2237061
• NM_004887.5:c.170+1794G>A

Variant summary

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

The NM_004887.5(CXCL14):​c.170+1794G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0848 in 152,194 control chromosomes in the GnomAD database, including 547 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 0.085 (547 hom., cov: 32)
• Consequence: CXCL14 NM_004887.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.324
• Publications: 5 publications found

Genes affected

CXCL14 (HGNC:10640): (C-X-C motif chemokine ligand 14) This antimicrobial gene belongs to the cytokine gene family which encode secreted proteins involved in immunoregulatory and inflammatory processes. The protein encoded by this gene is structurally related to the CXC (Cys-X-Cys) subfamily of cytokines. Members of this subfamily are characterized by two cysteines separated by a single amino acid. This cytokine displays chemotactic activity for monocytes but not for lymphocytes, dendritic cells, neutrophils or macrophages. It has been implicated that this cytokine is involved in the homeostasis of monocyte-derived macrophages rather than in inflammation. [provided by RefSeq, Sep 2014]

ENSG00000250167 (HGNC:):

SLC25A48 (HGNC:30451): (solute carrier family 25 member 48) Predicted to enable acyl carnitine transmembrane transporter activity. Predicted to be involved in acyl carnitine transport and amino acid transport. Predicted to be located in mitochondrial inner membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CXCL14	NM_004887.5	c.170+1794G>A		intron_variant	Intron 2 of 3	ENST00000512158.6	NP_004878.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CXCL14	ENST00000512158.6	c.170+1794G>A		intron_variant	Intron 2 of 3	1	NM_004887.5	ENSP00000423783.1

Frequencies

GnomAD3 genomes AF: 0.0848 AC: 12892 AN: 152076 Hom.: 546 Cov.: 32

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.0286

Gnomad AMR AF: 0.0607

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.151

Gnomad FIN AF: 0.0577

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0762

Gnomad OTH AF: 0.0823

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

GnomAD4 genome AF: 0.0848 AC: 12908 AN: 152194 Hom.: 547 Cov.: 32 AF XY: 0.0842 AC XY: 6269 AN XY: 74410

African (AFR) AF: 0.102 AC: 4252 AN: 41514

American (AMR) AF: 0.0605 AC: 926 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.128 AC: 444 AN: 3472

East Asian (EAS) AF: 0.105 AC: 543 AN: 5168

South Asian (SAS) AF: 0.150 AC: 726 AN: 4824

European-Finnish (FIN) AF: 0.0577 AC: 611 AN: 10596

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0762 AC: 5182 AN: 68010

Other (OTH) AF: 0.0814 AC: 172 AN: 2112

Alfa AF: 0.0800 Hom.: 848

Bravo AF: 0.0844

Asia WGS AF: 0.118 AC: 413 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.7
DANN	Benign	0.66
PhyloP100		-0.32
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: rs2237061; hg19: chr5-134912330;