rs2563298

Positions:

• chr5-140631730-C-A
• chr5-140631730-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000498971.7(CD14):​c.*126G>T variant causes a splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 866,530 control chromosomes in the GnomAD database, including 31,398 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.26 (5281 hom., cov: 32)
  • Exomes 𝑓: 0.26 (26117 hom.)
• Consequence: CD14 ENST00000498971.7 splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.443

Genes affected

CD14 (HGNC:1628): (CD14 molecule) The protein encoded by this gene is a surface antigen that is preferentially expressed on monocytes/macrophages. It cooperates with other proteins to mediate the innate immune response to bacterial lipopolysaccharide, and to viruses. This gene has been identified as a target candidate in the treatment of SARS-CoV-2-infected patients to potentially lessen or inhibit a severe inflammatory response. Alternative splicing results in multiple transcript variants encoding the same protein. [provided by RefSeq, Aug 2020]

TMCO6 (HGNC:28814): (transmembrane and coiled-coil domains 6) Predicted to enable nuclear import signal receptor activity. Predicted to be involved in protein import into nucleus. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD14	NM_000591.4	c.*126G>T		downstream_gene_variant		ENST00000302014.11	NP_000582.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD14	ENST00000302014.11	c.*126G>T		downstream_gene_variant		1	NM_000591.4	ENSP00000304236.6

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39290 AN: 152002 Hom.: 5282 Cov.: 32

Gnomad AFR AF: 0.221

Gnomad AMI AF: 0.150

Gnomad AMR AF: 0.266

Gnomad ASJ AF: 0.318

Gnomad EAS AF: 0.145

Gnomad SAS AF: 0.203

Gnomad FIN AF: 0.317

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.282

Gnomad OTH AF: 0.256

GnomAD4 exome AF: 0.263 AC: 188036 AN: 714410 Hom.: 26117 Cov.: 9 AF XY: 0.261 AC XY: 95965 AN XY: 367926

Gnomad4 AFR exome AF: 0.218

Gnomad4 AMR exome AF: 0.238

Gnomad4 ASJ exome AF: 0.325

Gnomad4 EAS exome AF: 0.160

Gnomad4 SAS exome AF: 0.191

Gnomad4 FIN exome AF: 0.319

Gnomad4 NFE exome AF: 0.275

Gnomad4 OTH exome AF: 0.259

GnomAD4 genome AF: 0.258 AC: 39307 AN: 152120 Hom.: 5281 Cov.: 32 AF XY: 0.261 AC XY: 19402 AN XY: 74346

Gnomad4 AFR AF: 0.221

Gnomad4 AMR AF: 0.266

Gnomad4 ASJ AF: 0.318

Gnomad4 EAS AF: 0.145

Gnomad4 SAS AF: 0.205

Gnomad4 FIN AF: 0.317

Gnomad4 NFE AF: 0.282

Gnomad4 OTH AF: 0.254

Alfa AF: 0.274 Hom.: 6469

Bravo AF: 0.250

Asia WGS AF: 0.187 AC: 648 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	2.7
DANN	Benign	0.68

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

Publications

LitVar

Other links and lift over

dbSNP: rs2563298; hg19: chr5-140011315; COSMIC: COSV57370632; COSMIC: COSV57370632;