Genetic Variant COL10A1:c.155-611A>T (chr6-116122572-T-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_000493.4(COL10A1):c.155-611A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.466 in 151,960 control chromosomes in the GnomAD database, including 18,498 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

Frequency

Genomes: 𝑓 0.47 ( 18498 hom., cov: 32)

Consequence

COL10A1
NM_000493.4 intron

Scores

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: -0.479

Publications

36 publications found

Variant links:

Genes affected

COL10A1 (HGNC:2185): (collagen type X alpha 1 chain) This gene encodes the alpha chain of type X collagen, a short chain collagen expressed by hypertrophic chondrocytes during endochondral ossification. Unlike type VIII collagen, the other short chain collagen, type X collagen is a homotrimer. Mutations in this gene are associated with Schmid type metaphyseal chondrodysplasia (SMCD) and Japanese type spondylometaphyseal dysplasia (SMD). [provided by RefSeq, Jul 2008]

COL10A1 links:

NT5DC1 (HGNC:21556): (5'-nucleotidase domain containing 1) While the exact function of the protein encoded by this gene is not known, it belongs to the 5'(3')-deoxyribonucleotidase family. [provided by RefSeq, May 2010]

NT5DC1 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=-0.86).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.709 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000493.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
COL10A1	NM_000493.4	MANE Select	c.155-611A>T	intron	N/A	NP_000484.2
NT5DC1	NM_152729.3	MANE Select	c.529+4627T>A	intron	N/A	NP_689942.2
COL10A1	NM_001424106.1		c.155-611A>T	intron	N/A	NP_001411035.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
COL10A1	ENST00000651968.1	MANE Select	c.155-611A>T	intron	N/A	ENSP00000498802.1
NT5DC1	ENST00000319550.9	TSL:1 MANE Select	c.529+4627T>A	intron	N/A	ENSP00000326858.3
COL10A1	ENST00000243222.8	TSL:1	c.155-611A>T	intron	N/A	ENSP00000243222.4

Frequencies

GnomAD3 genomes

AF:

0.466

AC:

70735

AN:

151842

Hom.:

18467

Cov.:

show subpopulations

Gnomad AFR

AF:

0.715

Gnomad AMI

AF:

0.243

Gnomad AMR

AF:

0.344

Gnomad ASJ

AF:

0.428

Gnomad EAS

AF:

0.233

Gnomad SAS

AF:

0.354

Gnomad FIN

AF:

0.358

Gnomad MID

AF:

0.462

Gnomad NFE

AF:

0.389

Gnomad OTH

AF:

0.451

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.466

AC:

70804

AN:

151960

Hom.:

18498

Cov.:

AF XY:

0.460

AC XY:

34171

AN XY:

74276

show subpopulations

African (AFR)

AF:

0.715

AC:

29647

AN:

41444

American (AMR)

AF:

0.344

AC:

5243

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.428

AC:

1482

AN:

3466

East Asian (EAS)

AF:

0.233

AC:

1199

AN:

5152

South Asian (SAS)

AF:

0.354

AC:

1707

AN:

4820

European-Finnish (FIN)

AF:

0.358

AC:

3773

AN:

10536

Middle Eastern (MID)

AF:

0.446

AC:

131

AN:

294

European-Non Finnish (NFE)

AF:

0.389

AC:

26446

AN:

67960

Other (OTH)

AF:

0.451

AC:

954

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1771

3542

5312

7083

8854

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

624

1248

1872

2496

3120

<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:

0.420

Hom.:

1717

Bravo

AF:

0.473

Asia WGS

AF:

0.389

AC:

1349

AN:

3476

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

LINK: link

Submissions by phenotype

not provided

Other:1

Department of Ophthalmology and Visual Sciences Kyoto University

Significance:not provided

Review Status:no classification provided

Collection Method:not provided

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.1

(source)

DANN

Benign

0.66

PhyloP100

-0.48

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over