rs5744456

Positions:

• chr5-140631764-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000591.4(CD14):​c.*92T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00221 in 1,186,312 control chromosomes in the GnomAD database, including 35 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 0.010 (19 hom., cov: 32)
  • Exomes 𝑓: 0.0010 (16 hom.)
• Consequence: CD14 NM_000591.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.123

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0102 (1552/152326) while in subpopulation AFR AF= 0.035 (1457/41574). AF 95% confidence interval is 0.0335. There are 19 homozygotes in gnomad4. There are 730 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 19 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD14	NM_000591.4	c.*92T>A		3_prime_UTR_variant	2/2	ENST00000302014.11	NP_000582.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD14	ENST00000302014.11	c.*92T>A		3_prime_UTR_variant	2/2	1	NM_000591.4	ENSP00000304236	P1
CD14	ENST00000498971.7	c.*92T>A		3_prime_UTR_variant	3/3	2		ENSP00000426543	P1
CD14	ENST00000512545.2	c.*92T>A		3_prime_UTR_variant	3/3	3		ENSP00000425447	P1
CD14	ENST00000519715.2	c.*92T>A		3_prime_UTR_variant	3/3	4		ENSP00000430884	P1

Frequencies

GnomAD3 genomes AF: 0.0102 AC: 1552 AN: 152208 Hom.: 19 Cov.: 32

Gnomad AFR AF: 0.0351

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00484

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00573

GnomAD4 exome AF: 0.00103 AC: 1068 AN: 1033986 Hom.: 16 Cov.: 13 AF XY: 0.000896 AC XY: 463 AN XY: 516550

Gnomad4 AFR exome AF: 0.0337

Gnomad4 AMR exome AF: 0.00154

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000330

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000885

Gnomad4 OTH exome AF: 0.00279

GnomAD4 genome AF: 0.0102 AC: 1552 AN: 152326 Hom.: 19 Cov.: 32 AF XY: 0.00980 AC XY: 730 AN XY: 74484

Gnomad4 AFR AF: 0.0350

Gnomad4 AMR AF: 0.00483

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.00567

Alfa AF: 0.00707 Hom.: 2

Bravo AF: 0.0116

Asia WGS AF: 0.00318 AC: 11 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	11
DANN	Benign	0.76

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: rs5744456; hg19: chr5-140011349;