Genetic Variant CD14:c.-121-139T>C (chr5-140633331-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001040021.3(CD14):c.-121-139T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.532 in 598,992 control chromosomes in the GnomAD database, including 86,070 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 0.57 ( 24871 hom., cov: 31)

Exomes 𝑓: 0.52 ( 61199 hom. )

Consequence

CD14
NM_001040021.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.07

Publications

618 publications found

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:28814): (transmembrane and coiled-coil domains 6) Predicted to enable nuclear import signal receptor activity. Predicted to be involved in protein import into nucleus. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMCO6 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.666 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001040021.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein	UniProt
CD14	NM_001040021.3	c.-121-139T>C	intron	N/A	NP_001035110.1	P08571
CD14	NM_001174104.2	c.-221-39T>C	intron	N/A	NP_001167575.1	P08571
CD14	NM_001174105.2	c.-121-139T>C	intron	N/A	NP_001167576.1	P08571

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CD14	ENST00000498971.7	TSL:2	c.-121-139T>C	intron	N/A	ENSP00000426543.2	P08571
CD14	ENST00000512545.2	TSL:3	c.-221-39T>C	intron	N/A	ENSP00000425447.2	P08571
CD14	ENST00000519715.2	TSL:4	c.-121-139T>C	intron	N/A	ENSP00000430884.2	P08571

Frequencies

GnomAD3 genomes

AF:

0.566

AC:

85846

AN:

151726

Hom.:

24820

Cov.:

show subpopulations

Gnomad AFR

AF:

0.672

Gnomad AMI

AF:

0.204

Gnomad AMR

AF:

0.529

Gnomad ASJ

AF:

0.529

Gnomad EAS

AF:

0.443

Gnomad SAS

AF:

0.466

Gnomad FIN

AF:

0.626

Gnomad MID

AF:

0.430

Gnomad NFE

AF:

0.524

Gnomad OTH

AF:

0.545

GnomAD4 exome

AF:

0.520

AC:

232594

AN:

447148

Hom.:

61199

Cov.:

AF XY:

0.515

AC XY:

121968

AN XY:

237050

show subpopulations

African (AFR)

AF:

0.660

AC:

8348

AN:

12656

American (AMR)

AF:

0.507

AC:

10712

AN:

21142

Ashkenazi Jewish (ASJ)

AF:

0.529

AC:

7329

AN:

13844

East Asian (EAS)

AF:

0.448

AC:

13453

AN:

30012

South Asian (SAS)

AF:

0.449

AC:

21493

AN:

47902

European-Finnish (FIN)

AF:

0.615

AC:

17213

AN:

27980

Middle Eastern (MID)

AF:

0.493

AC:

943

AN:

1914

European-Non Finnish (NFE)

AF:

0.524

AC:

139523

AN:

266088

Other (OTH)

AF:

0.530

AC:

13580

AN:

25610

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

5588

11176

16763

22351

27939

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

712

1424

2136

2848

3560

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.566

AC:

85953

AN:

151844

Hom.:

24871

Cov.:

AF XY:

0.568

AC XY:

42170

AN XY:

74194

show subpopulations

African (AFR)

AF:

0.672

AC:

27828

AN:

41384

American (AMR)

AF:

0.530

AC:

8088

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.529

AC:

1833

AN:

3468

East Asian (EAS)

AF:

0.443

AC:

2282

AN:

5152

South Asian (SAS)

AF:

0.467

AC:

2250

AN:

4820

European-Finnish (FIN)

AF:

0.626

AC:

6582

AN:

10518

Middle Eastern (MID)

AF:

0.425

AC:

125

AN:

294

European-Non Finnish (NFE)

AF:

0.525

AC:

35625

AN:

67918

Other (OTH)

AF:

0.547

AC:

1154

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

1921

3842

5763

7684

9605

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

724

1448

2172

2896

3620

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.531

Hom.:

34727

Bravo

AF:

0.559

Asia WGS

AF:

0.524

AC:

1820

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.0

(source)

DANN

Benign

0.46

PhyloP100

-1.1

PromoterAI

0.15

Neutral

(source)

Mutation Taster

=297/3

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over