dbSNP rs2563298: CD14:c.*126G>T (chr5-140631730-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000498971.7(CD14):c.*126G>T variant causes a splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 866,530 control chromosomes in the GnomAD database, including 31,398 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.26 ( 5281 hom., cov: 32)

Exomes 𝑓: 0.26 ( 26117 hom. )

Consequence

CD14
ENST00000498971.7 splice_region

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.443

Publications

31 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:

Genome browser will be placed here

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=-0.77).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD14	NM_000591.4 link	c.*126G>T		downstream_gene_variant		ENST00000302014.11	NP_000582.1	P08571

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD14	ENST00000302014.11 link	c.*126G>T		downstream_gene_variant		1	NM_000591.4	ENSP00000304236.6		P08571

Frequencies

GnomAD3 genomes

AF:

0.258

AC:

39290

AN:

152002

Hom.:

5282

Cov.:

show subpopulations

Gnomad AFR

AF:

0.221

Gnomad AMI

AF:

0.150

Gnomad AMR

AF:

0.266

Gnomad ASJ

AF:

0.318

Gnomad EAS

AF:

0.145

Gnomad SAS

AF:

0.203

Gnomad FIN

AF:

0.317

Gnomad MID

AF:

0.253

Gnomad NFE

AF:

0.282

Gnomad OTH

AF:

0.256

GnomAD4 exome

AF:

0.263

AC:

188036

AN:

714410

Hom.:

26117

Cov.:

AF XY:

0.261

AC XY:

95965

AN XY:

367926

show subpopulations

African (AFR)

AF:

0.218

AC:

3927

AN:

18018

American (AMR)

AF:

0.238

AC:

6467

AN:

27198

Ashkenazi Jewish (ASJ)

AF:

0.325

AC:

5053

AN:

15540

East Asian (EAS)

AF:

0.160

AC:

5718

AN:

35702

South Asian (SAS)

AF:

0.191

AC:

10207

AN:

53402

European-Finnish (FIN)

AF:

0.319

AC:

15230

AN:

47752

Middle Eastern (MID)

AF:

0.299

AC:

1061

AN:

3554

European-Non Finnish (NFE)

AF:

0.275

AC:

131409

AN:

478616

Other (OTH)

AF:

0.259

AC:

8964

AN:

34628

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

6930

13861

20791

27722

34652

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2784

5568

8352

11136

13920

<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:

0.258

AC:

39307

AN:

152120

Hom.:

5281

Cov.:

AF XY:

0.261

AC XY:

19402

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.221

AC:

9161

AN:

41514

American (AMR)

AF:

0.266

AC:

4068

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.318

AC:

1104

AN:

3472

East Asian (EAS)

AF:

0.145

AC:

751

AN:

5174

South Asian (SAS)

AF:

0.205

AC:

985

AN:

4816

European-Finnish (FIN)

AF:

0.317

AC:

3348

AN:

10564

Middle Eastern (MID)

AF:

0.255

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.282

AC:

19143

AN:

67982

Other (OTH)

AF:

0.254

AC:

535

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1528

3056

4583

6111

7639

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

410

820

1230

1640

2050

<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:

0.270

Hom.:

16730

Bravo

AF:

0.250

Asia WGS

AF:

0.187

AC:

648

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

2.7

(source)

DANN

Benign

0.68

PhyloP100

-0.44

Mutation Taster

=100/0

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over