Genetic Variant XM_011537665.3:c.-129-7943G>A (chr5-140633722-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The XM_011537665.3(TMCO6):c.-129-7943G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 151,962 control chromosomes in the GnomAD database, including 3,374 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 0.19 ( 3358 hom., cov: 31)

Exomes 𝑓: 0.16 ( 16 hom. )

Consequence

TMCO6
XM_011537665.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0480

Publications

47 publications found

Variant links:

Genes affected

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:

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:

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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=-0.81).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000498971.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein
CD14	NM_001040021.3	c.-313C>T	upstream_gene	N/A	NP_001035110.1
CD14	NM_001174104.2	c.-413C>T	upstream_gene	N/A	NP_001167575.1
CD14	NM_001174105.2	c.-292C>T	upstream_gene	N/A	NP_001167576.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CD14	ENST00000498971.7	TSL:2	c.-313C>T	upstream_gene	N/A	ENSP00000426543.2
CD14	ENST00000512545.2	TSL:3	c.-413C>T	upstream_gene	N/A	ENSP00000425447.2
CD14	ENST00000519715.2	TSL:4	c.-292C>T	upstream_gene	N/A	ENSP00000430884.2

Frequencies

GnomAD3 genomes

AF:

0.194

AC:

29277

AN:

151264

Hom.:

3345

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0819

Gnomad AMI

AF:

0.0540

Gnomad AMR

AF:

0.215

Gnomad ASJ

AF:

0.202

Gnomad EAS

AF:

0.296

Gnomad SAS

AF:

0.257

Gnomad FIN

AF:

0.285

Gnomad MID

AF:

0.125

Gnomad NFE

AF:

0.232

Gnomad OTH

AF:

0.191

GnomAD4 exome

AF:

0.163

AC:

AN:

594

Hom.:

Cov.:

AF XY:

0.139

AC XY:

AN XY:

280

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.128

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.333

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.214

AC:

AN:

European-Finnish (FIN)

AF:

0.125

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.172

AC:

AN:

402

Other (OTH)

AF:

0.105

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.194

AC:

29298

AN:

151368

Hom.:

3358

Cov.:

AF XY:

0.196

AC XY:

14462

AN XY:

73900

show subpopulations

African (AFR)

AF:

0.0816

AC:

3369

AN:

41270

American (AMR)

AF:

0.216

AC:

3280

AN:

15208

Ashkenazi Jewish (ASJ)

AF:

0.202

AC:

700

AN:

3468

East Asian (EAS)

AF:

0.296

AC:

1523

AN:

5150

South Asian (SAS)

AF:

0.257

AC:

1230

AN:

4792

European-Finnish (FIN)

AF:

0.285

AC:

2943

AN:

10334

Middle Eastern (MID)

AF:

0.115

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.232

AC:

15759

AN:

67852

Other (OTH)

AF:

0.196

AC:

412

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1139

2278

3418

4557

5696

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

302

604

906

1208

1510

<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:

0.213

Hom.:

8264

Bravo

AF:

0.181

Asia WGS

AF:

0.312

AC:

1085

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

5.8

(source)

DANN

Benign

0.69

PhyloP100

0.048

PromoterAI

-0.018

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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