rs2547

Positions:

• chr5-135571862-G-A
• chr5-135571862-G-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_004887.5(CXCL14):​c.291C>T​(p.Tyr97=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0906 in 1,582,688 control chromosomes in the GnomAD database, including 6,958 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 0.088 (498 hom., cov: 29)
  • Exomes 𝑓: 0.091 (6460 hom.)
• Consequence: CXCL14 NM_004887.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.132

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]

(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

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP7: Synonymous conserved (PhyloP=0.132 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.153 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CXCL14	NM_004887.5	c.291C>T	p.Tyr97=	synonymous_variant	4/4	ENST00000512158.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CXCL14	ENST00000512158.6	c.291C>T	p.Tyr97=	synonymous_variant	4/4	1	NM_004887.5	P1
	ENST00000698884.1	n.497-57375G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0881 AC: 12509 AN: 141930 Hom.: 497 Cov.: 29

Gnomad AFR AF: 0.0874

Gnomad AMI AF: 0.0290

Gnomad AMR AF: 0.0674

Gnomad ASJ AF: 0.129

Gnomad EAS AF: 0.116

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.0737

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0861

Gnomad OTH AF: 0.0892

GnomAD3 exomes AF: 0.0885 AC: 22177 AN: 250638 Hom.: 1212 AF XY: 0.0932 AC XY: 12621 AN XY: 135464

Gnomad AFR exome AF: 0.0822

Gnomad AMR exome AF: 0.0415

Gnomad ASJ exome AF: 0.113

Gnomad EAS exome AF: 0.105

Gnomad SAS exome AF: 0.161

Gnomad FIN exome AF: 0.0621

Gnomad NFE exome AF: 0.0847

Gnomad OTH exome AF: 0.0826

GnomAD4 exome AF: 0.0908 AC: 130834 AN: 1440666 Hom.: 6460 Cov.: 32 AF XY: 0.0934 AC XY: 66901 AN XY: 716630

Gnomad4 AFR exome AF: 0.0808

Gnomad4 AMR exome AF: 0.0434

Gnomad4 ASJ exome AF: 0.118

Gnomad4 EAS exome AF: 0.0851

Gnomad4 SAS exome AF: 0.156

Gnomad4 FIN exome AF: 0.0646

Gnomad4 NFE exome AF: 0.0883

Gnomad4 OTH exome AF: 0.100

GnomAD4 genome AF: 0.0882 AC: 12523 AN: 142022 Hom.: 498 Cov.: 29 AF XY: 0.0894 AC XY: 6102 AN XY: 68284

Gnomad4 AFR AF: 0.0877

Gnomad4 AMR AF: 0.0673

Gnomad4 ASJ AF: 0.129

Gnomad4 EAS AF: 0.116

Gnomad4 SAS AF: 0.163

Gnomad4 FIN AF: 0.0737

Gnomad4 NFE AF: 0.0861

Gnomad4 OTH AF: 0.0883

Alfa AF: 0.0867 Hom.: 643

Bravo AF: 0.0809

Asia WGS AF: 0.117 AC: 411 AN: 3478

EpiCase AF: 0.0886

EpiControl AF: 0.0900

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	5.2
DANN	Benign	0.87

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.19		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: rs2547; hg19: chr5-134907552;