rs5744455

Positions:

• chr5-140633722-G-A
• chr5-140633722-G-T

Variant summary

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

The XM_011537665.3(TMCO6):​c.-129-7943G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 151,962 control chromosomes in the GnomAD database, including 3,374 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 0.19 (3358 hom., cov: 31)
  • Exomes 𝑓: 0.16 (16 hom.)
• Consequence: TMCO6 XM_011537665.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0480

Genes affected

TMCO6 (HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMCO6	XM_011537665.3	c.-129-7943G>A		intron_variant			XP_011535967.1
TMCO6	XM_024446125.2	c.-472-6017G>A		intron_variant			XP_024301893.1
TMCO6	XM_047417355.1	c.-242-6017G>A		intron_variant			XP_047273311.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD14	ENST00000512545.2			upstream_gene_variant		3		ENSP00000425447	P1
CD14	ENST00000519715.2			upstream_gene_variant		4		ENSP00000430884	P1

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29277 AN: 151264 Hom.: 3345 Cov.: 31

Gnomad AFR AF: 0.0819

Gnomad AMI AF: 0.0540

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.296

Gnomad SAS AF: 0.257

Gnomad FIN AF: 0.285

Gnomad MID AF: 0.125

Gnomad NFE AF: 0.232

Gnomad OTH AF: 0.191

GnomAD4 exome AF: 0.163 AC: 97 AN: 594 Hom.: 16 Cov.: 0 AF XY: 0.139 AC XY: 39 AN XY: 280

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.128

Gnomad4 ASJ exome AF: 0.333

Gnomad4 SAS exome AF: 0.214

Gnomad4 FIN exome AF: 0.125

Gnomad4 NFE exome AF: 0.172

Gnomad4 OTH exome AF: 0.105

GnomAD4 genome AF: 0.194 AC: 29298 AN: 151368 Hom.: 3358 Cov.: 31 AF XY: 0.196 AC XY: 14462 AN XY: 73900

Gnomad4 AFR AF: 0.0816

Gnomad4 AMR AF: 0.216

Gnomad4 ASJ AF: 0.202

Gnomad4 EAS AF: 0.296

Gnomad4 SAS AF: 0.257

Gnomad4 FIN AF: 0.285

Gnomad4 NFE AF: 0.232

Gnomad4 OTH AF: 0.196

Alfa AF: 0.219 Hom.: 4447

Bravo AF: 0.181

Asia WGS AF: 0.312 AC: 1085 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.8
DANN	Benign	0.69

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs5744455; hg19: chr5-140013307;