Genetic Variant NM_004370.6:c.2710+1689A>G (chr6-75173349-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_004370.6(COL12A1):c.2710+1689A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.074 in 152,234 control chromosomes in the GnomAD database, including 709 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 0.074 ( 709 hom., cov: 32)

Consequence

COL12A1
NM_004370.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.04

Publications

2 publications found

Variant links:

Genes affected

COL12A1 (HGNC:2188): (collagen type XII alpha 1 chain) This gene encodes the alpha chain of type XII collagen, a member of the FACIT (fibril-associated collagens with interrupted triple helices) collagen family. Type XII collagen is a homotrimer found in association with type I collagen, an association that is thought to modify the interactions between collagen I fibrils and the surrounding matrix. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

COL12A1 Gene-Disease associations (from GenCC):

Ullrich congenital muscular dystrophy 2
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), LiferaOmics
Bethlem myopathy 2
Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)
Bethlem myopathy 2
Inheritance: AD Classification: STRONG, LIMITED Submitted by: Genomics England PanelApp, Ambry Genetics, Illumina
Bethlem myopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Ullrich congenital muscular dystrophy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

COL12A1 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_004370.6, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.94).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004370.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
COL12A1	NM_004370.6	MANE Select	c.2710+1689A>G	intron	N/A	NP_004361.3
COL12A1	NM_001424113.1		c.2710+1689A>G	intron	N/A	NP_001411042.1
COL12A1	NM_001424114.1		c.2710+1689A>G	intron	N/A	NP_001411043.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
COL12A1	ENST00000322507.13	TSL:1 MANE Select	c.2710+1689A>G	intron	N/A	ENSP00000325146.8	Q99715-1
COL12A1	ENST00000345356.10	TSL:1	c.74-20867A>G	intron	N/A	ENSP00000305147.9	Q99715-2
COL12A1	ENST00000483888.6	TSL:5	c.2710+1689A>G	intron	N/A	ENSP00000421216.1	D6RGG3

Frequencies

GnomAD3 genomes

AF:

0.0736

AC:

11196

AN:

152116

Hom.:

690

Cov.:

show subpopulations

Gnomad AFR

AF:

0.139

Gnomad AMI

AF:

0.0164

Gnomad AMR

AF:

0.0875

Gnomad ASJ

AF:

0.0562

Gnomad EAS

AF:

0.222

Gnomad SAS

AF:

0.121

Gnomad FIN

AF:

0.0282

Gnomad MID

AF:

0.0791

Gnomad NFE

AF:

0.0251

Gnomad OTH

AF:

0.0700

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

GnomAD4 genome

AF:

0.0740

AC:

11262

AN:

152234

Hom.:

709

Cov.:

AF XY:

0.0760

AC XY:

5656

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.140

AC:

5800

AN:

41548

American (AMR)

AF:

0.0883

AC:

1350

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0562

AC:

195

AN:

3468

East Asian (EAS)

AF:

0.222

AC:

1148

AN:

5168

South Asian (SAS)

AF:

0.120

AC:

581

AN:

4824

European-Finnish (FIN)

AF:

0.0282

AC:

299

AN:

10600

Middle Eastern (MID)

AF:

0.0816

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0251

AC:

1706

AN:

68018

Other (OTH)

AF:

0.0683

AC:

144

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

519

1038

1558

2077

2596

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

126

252

378

504

630

<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:

0.0560

Hom.:

Bravo

AF:

0.0814

Asia WGS

AF:

0.164

AC:

570

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.054

(source)

DANN

Benign

0.45

PhyloP100

-3.0

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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

Computational scores

Splicing

Publications

Other links and lift over