rs10484915

Variant names:

• chr6-75173349-T-C
• rs10484915
• NM_004370.6:c.2710+1689A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.04
• Publications: 2 publications found

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):

• Bethlem myopathy 2

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet
• Bethlem myopathy 2

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Illumina, Genomics England PanelApp
• Ullrich congenital muscular dystrophy 2

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• Bethlem myopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Ullrich congenital muscular dystrophy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL12A1	NM_004370.6	c.2710+1689A>G		intron_variant	Intron 13 of 65	ENST00000322507.13	NP_004361.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL12A1	ENST00000322507.13	c.2710+1689A>G		intron_variant	Intron 13 of 65	1	NM_004370.6	ENSP00000325146.8
COL12A1	ENST00000345356.10	c.74-20867A>G		intron_variant	Intron 2 of 50	1		ENSP00000305147.9
COL12A1	ENST00000483888.6	c.2710+1689A>G		intron_variant	Intron 13 of 64	5		ENSP00000421216.1
COL12A1	ENST00000416123.6	c.2710+1689A>G		intron_variant	Intron 12 of 62	5		ENSP00000412864.2

Frequencies

GnomAD3 genomes AF: 0.0736 AC: 11196 AN: 152116 Hom.: 690 Cov.: 32

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.: 32 AF XY: 0.0760 AC XY: 5656 AN XY: 74440

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: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0251 AC: 1706 AN: 68018

Other (OTH) AF: 0.0683 AC: 144 AN: 2108

Alfa AF: 0.0560 Hom.: 63

Bravo AF: 0.0814

Asia WGS AF: 0.164 AC: 570 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.054
DANN	Benign	0.45
PhyloP100		-3.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10484915; hg19: chr6-75883065;