Variant 5-140632282-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0500

Variant links:

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]

CD14 links:

TMCO6 (HGNC:):

TMCO6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 GnomAd4 at 9 gene

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes

AF:

0.00205

AC:

312

AN:

152244

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.00482

AC XY:

654

AN XY:

135556

show subpopulations

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.:

Cov.:

AF XY:

0.00158

AC XY:

1152

AN XY:

727126

show subpopulations

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.:

Cov.:

AF XY:

0.00230

AC XY:

171

AN XY:

74506

show subpopulations

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.:

Bravo

AF:

0.00260

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00460

AC:

558

Asia WGS

AF:

0.0180

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.31

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.089

T;T

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.64

FATHMM_MKL

Benign

0.048

LIST_S2

Benign

0.63

.;T

MetaRNN

Benign

0.0021

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.97

L;L

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.48

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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over