rs77083413

chr5-140631967-G-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BS1 BS2

The NM_000591.4(CD14):c.1017C>G(p.Pro339=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000793 in 1,613,710 control chromosomes in the GnomAD database, including 18 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 0.00062 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00081 (16 hom.)
• Consequence: CD14 NM_000591.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.440

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP7: Synonymous conserved (PhyloP=-0.44 with no splicing effect.
• BS1: Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.000812 (1186/1461424) while in subpopulation EAS AF= 0.0242 (961/39680). AF 95% confidence interval is 0.0229. There are 16 homozygotes in gnomad4_exome. There are 623 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD14	NM_000591.4	c.1017C>G	p.Pro339=	synonymous_variant	2/2	ENST00000302014.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD14	ENST00000302014.11	c.1017C>G	p.Pro339=	synonymous_variant	2/2	1	NM_000591.4	P1
CD14	ENST00000498971.7	c.1017C>G	p.Pro339=	synonymous_variant	3/3	2		P1
CD14	ENST00000512545.2	c.1017C>G	p.Pro339=	synonymous_variant	3/3	3		P1
CD14	ENST00000519715.2	c.1017C>G	p.Pro339=	synonymous_variant	3/3	4		P1

Frequencies

GnomAD3 genomes AF: 0.000618 AC: 94 AN: 152168 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0150

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000988 AC: 248 AN: 251022 Hom.: 3 AF XY: 0.00101 AC XY: 137 AN XY: 135736

Gnomad AFR exome AF: 0.0000617

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0115

Gnomad SAS exome AF: 0.000588

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000106

Gnomad OTH exome AF: 0.000981

GnomAD4 exome AF: 0.000812 AC: 1186 AN: 1461424 Hom.: 16 Cov.: 32 AF XY: 0.000857 AC XY: 623 AN XY: 726944

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0242

Gnomad4 SAS exome AF: 0.000557

Gnomad4 FIN exome AF: 0.0000562

Gnomad4 NFE exome AF: 0.000119

Gnomad4 OTH exome AF: 0.000662

GnomAD4 genome AF: 0.000617 AC: 94 AN: 152286 Hom.: 2 Cov.: 32 AF XY: 0.000739 AC XY: 55 AN XY: 74458

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000654

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0151

Gnomad4 SAS AF: 0.000830

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000147

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000246 Hom.: 0

Bravo AF: 0.000446

Asia WGS AF: 0.00462 AC: 16 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	1.8
Dann	Benign	0.40
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs77083413; hg19: chr5-140011552;