chr5-140631967-G-C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BS1BS2

The NM_000591.4(CD14):​c.1017C>G​(p.Pro339Pro) 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

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.440

Publications

3 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]
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]

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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. GnomAdExome4 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 GnomAdExome4. There are 623 alleles in the male GnomAdExome4 subpopulation. Median coverage is 32. This position passed quality control check.
BS2
High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CD14NM_000591.4 linkc.1017C>G p.Pro339Pro synonymous_variant Exon 2 of 2 ENST00000302014.11 NP_000582.1 P08571

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CD14ENST00000302014.11 linkc.1017C>G p.Pro339Pro synonymous_variant Exon 2 of 2 1 NM_000591.4 ENSP00000304236.6 P08571
CD14ENST00000498971.7 linkc.1017C>G p.Pro339Pro synonymous_variant Exon 3 of 3 2 ENSP00000426543.2 P08571D6RFL4
CD14ENST00000512545.2 linkc.1017C>G p.Pro339Pro synonymous_variant Exon 3 of 3 3 ENSP00000425447.2 P08571D6RD81
CD14ENST00000519715.2 linkc.1017C>G p.Pro339Pro synonymous_variant Exon 3 of 3 4 ENSP00000430884.2 P08571E7EVL5

Frequencies

GnomAD3 genomes
AF:
0.000618
AC:
94
AN:
152168
Hom.:
2
Cov.:
32
show subpopulations
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
GnomAD2 exomes
AF:
0.000988
AC:
248
AN:
251022
AF XY:
0.00101
show subpopulations
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 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
show subpopulations
African (AFR)
AF:
0.0000299
AC:
1
AN:
33476
American (AMR)
AF:
0.00
AC:
0
AN:
44716
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26130
East Asian (EAS)
AF:
0.0242
AC:
961
AN:
39680
South Asian (SAS)
AF:
0.000557
AC:
48
AN:
86246
European-Finnish (FIN)
AF:
0.0000562
AC:
3
AN:
53400
Middle Eastern (MID)
AF:
0.000173
AC:
1
AN:
5766
European-Non Finnish (NFE)
AF:
0.000119
AC:
132
AN:
1111632
Other (OTH)
AF:
0.000662
AC:
40
AN:
60378
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.491
Heterozygous variant carriers
0
76
153
229
306
382
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
20
40
60
80
100
<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:
0.000617
AC:
94
AN:
152286
Hom.:
2
Cov.:
32
AF XY:
0.000739
AC XY:
55
AN XY:
74458
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
41566
American (AMR)
AF:
0.0000654
AC:
1
AN:
15300
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3472
East Asian (EAS)
AF:
0.0151
AC:
78
AN:
5180
South Asian (SAS)
AF:
0.000830
AC:
4
AN:
4820
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10602
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
0.000147
AC:
10
AN:
68024
Other (OTH)
AF:
0.000473
AC:
1
AN:
2116
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.501
Heterozygous variant carriers
0
4
9
13
18
22
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
2
4
6
8
10
<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:
0.000246
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
PhyloP100
-0.44
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Mutation Taster
=100/0
polymorphism

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

Other links and lift over

dbSNP: rs77083413; hg19: chr5-140011552; API