5-140632282-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_000591.4(CD14):c.702G>A(p.Met234Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00155 in 1,613,928 control chromosomes in the GnomAD database, including 56 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0021 (9 hom., cov: 32)
  • Exomes 𝑓: 0.0015 (47 hom.)
• Consequence: CD14 NM_000591.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0500

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0020824373).
• BP6: Variant 5-140632282-C-T is Benign according to our data. Variant chr5-140632282-C-T is described in ClinVar as [Benign]. Clinvar id is 715333.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00205 (313/152362) while in subpopulation EAS AF= 0.0506 (262/5176). AF 95% confidence interval is 0.0456. There are 9 homozygotes in gnomad4. There are 171 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 9 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD14	NM_000591.4	c.702G>A	p.Met234Ile	missense_variant	2/2	ENST00000302014.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD14	ENST00000302014.11	c.702G>A	p.Met234Ile	missense_variant	2/2	1	NM_000591.4	P1
CD14	ENST00000498971.7	c.702G>A	p.Met234Ile	missense_variant	3/3	2		P1
CD14	ENST00000512545.2	c.702G>A	p.Met234Ile	missense_variant	3/3	3		P1
CD14	ENST00000519715.2	c.702G>A	p.Met234Ile	missense_variant	3/3	4		P1

Frequencies

GnomAD3 genomes AF: 0.00205 AC: 312 AN: 152244 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.000265

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000392

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.0503

Gnomad SAS AF: 0.00393

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00478

GnomAD3 exomes AF: 0.00509 AC: 1275 AN: 250248 Hom.: 30 AF XY: 0.00482 AC XY: 654 AN XY: 135556

Gnomad AFR exome AF: 0.000376

Gnomad AMR exome AF: 0.0000867

Gnomad ASJ exome AF: 0.000697

Gnomad EAS exome AF: 0.0649

Gnomad SAS exome AF: 0.00134

Gnomad FIN exome AF: 0.0000466

Gnomad NFE exome AF: 0.0000796

Gnomad OTH exome AF: 0.00262

GnomAD4 exome AF: 0.00150 AC: 2196 AN: 1461566 Hom.: 47 Cov.: 32 AF XY: 0.00158 AC XY: 1152 AN XY: 727126

Gnomad4 AFR exome AF: 0.000149

Gnomad4 AMR exome AF: 0.0000894

Gnomad4 ASJ exome AF: 0.00115

Gnomad4 EAS exome AF: 0.0429

Gnomad4 SAS exome AF: 0.00217

Gnomad4 FIN exome AF: 0.0000188

Gnomad4 NFE exome AF: 0.0000414

Gnomad4 OTH exome AF: 0.00358

GnomAD4 genome AF: 0.00205 AC: 313 AN: 152362 Hom.: 9 Cov.: 32 AF XY: 0.00230 AC XY: 171 AN XY: 74506

Gnomad4 AFR AF: 0.000265

Gnomad4 AMR AF: 0.000392

Gnomad4 ASJ AF: 0.000865

Gnomad4 EAS AF: 0.0506

Gnomad4 SAS AF: 0.00393

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00473

Alfa AF: 0.00181 Hom.: 9

Bravo AF: 0.00260

ESP6500AA AF: 0.000681 AC: 3

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00460 AC: 558

Asia WGS AF: 0.0180 AC: 63 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 11, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.64
Cadd	Benign	14
Dann	Benign	0.97
DEOGEN2	Benign	0.089	T;T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.048	N
MetaRNN	Benign	0.0021	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.97	L;L
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-0.75	N;N
REVEL	Benign	0.056
Sift	Benign	0.087	T;T
Sift4G	Benign	0.10	T;T
Polyphen		0.032	B;B
Vest4		0.14
MutPred		0.54		Loss of disorder (P = 0.1674);Loss of disorder (P = 0.1674);
MVP		0.32
MPC		0.59
ClinPred		0.0094	T
GERP RS		1.9
Varity_R		0.42
gMVP		0.22

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: rs74587733; hg19: chr5-140011867;