5-140633331-A-G

Position:

• chr5-140633331-A-G

Variant summary

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

The NM_001040021.3(CD14):​c.-121-139T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.532 in 598,992 control chromosomes in the GnomAD database, including 86,070 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 0.57 (24871 hom., cov: 31)
  • Exomes 𝑓: 0.52 (61199 hom.)
• Consequence: CD14 NM_001040021.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.666 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD14	NM_001040021.3	c.-121-139T>C		intron_variant			NP_001035110.1
CD14	NM_001174104.2	c.-221-39T>C		intron_variant			NP_001167575.1
CD14	NM_001174105.2	c.-121-139T>C		intron_variant			NP_001167576.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD14	ENST00000498971.7	c.-121-139T>C		intron_variant		2		ENSP00000426543.2
CD14	ENST00000512545.2	c.-221-39T>C		intron_variant		3		ENSP00000425447.2
CD14	ENST00000519715.2	c.-121-139T>C		intron_variant		4		ENSP00000430884.2

Frequencies

GnomAD3 genomes AF: 0.566 AC: 85846 AN: 151726 Hom.: 24820 Cov.: 31

Gnomad AFR AF: 0.672

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.529

Gnomad ASJ AF: 0.529

Gnomad EAS AF: 0.443

Gnomad SAS AF: 0.466

Gnomad FIN AF: 0.626

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.524

Gnomad OTH AF: 0.545

GnomAD4 exome AF: 0.520 AC: 232594 AN: 447148 Hom.: 61199 Cov.: 4 AF XY: 0.515 AC XY: 121968 AN XY: 237050

Gnomad4 AFR exome AF: 0.660

Gnomad4 AMR exome AF: 0.507

Gnomad4 ASJ exome AF: 0.529

Gnomad4 EAS exome AF: 0.448

Gnomad4 SAS exome AF: 0.449

Gnomad4 FIN exome AF: 0.615

Gnomad4 NFE exome AF: 0.524

Gnomad4 OTH exome AF: 0.530

GnomAD4 genome AF: 0.566 AC: 85953 AN: 151844 Hom.: 24871 Cov.: 31 AF XY: 0.568 AC XY: 42170 AN XY: 74194

Gnomad4 AFR AF: 0.672

Gnomad4 AMR AF: 0.530

Gnomad4 ASJ AF: 0.529

Gnomad4 EAS AF: 0.443

Gnomad4 SAS AF: 0.467

Gnomad4 FIN AF: 0.626

Gnomad4 NFE AF: 0.525

Gnomad4 OTH AF: 0.547

Alfa AF: 0.518 Hom.: 16476

Bravo AF: 0.559

Asia WGS AF: 0.524 AC: 1820 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.0
DANN	Benign	0.46

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: rs2569190; hg19: chr5-140012916; COSMIC: COSV57371477;