rs752652515

Positions:

• chr6-75181216-T-TA
• chr6-75181216-T-TAA
• chr6-75181216-T-TC

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_004370.6(COL12A1):​c.1892-6_1892-5insT variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000668 in 1,406,404 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00043 (0 hom., cov: 25)
  • Exomes 𝑓: 0.000062 (0 hom.)
• Consequence: COL12A1 NM_004370.6 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.52

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP6: Variant 6-75181216-T-TA is Benign according to our data. Variant chr6-75181216-T-TA is described in ClinVar as [Benign]. Clinvar id is 1165668.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL12A1	NM_004370.6	c.1892-6_1892-5insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000322507.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL12A1	ENST00000322507.13	c.1892-6_1892-5insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_004370.6	P4

Frequencies

GnomAD3 genomes AF: 0.000430 AC: 8 AN: 18588 Hom.: 0 Cov.: 25

Gnomad AFR AF: 0.000313

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00410

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00147

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000596

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000194 AC: 20 AN: 103032 Hom.: 0 AF XY: 0.000180 AC XY: 10 AN XY: 55584

Gnomad AFR exome AF: 0.000311

Gnomad AMR exome AF: 0.000256

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000107

Gnomad SAS exome AF: 0.000101

Gnomad FIN exome AF: 0.000111

Gnomad NFE exome AF: 0.000208

Gnomad OTH exome AF: 0.000419

GnomAD4 exome AF: 0.0000620 AC: 86 AN: 1387792 Hom.: 0 Cov.: 28 AF XY: 0.0000770 AC XY: 53 AN XY: 688080

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000897

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000262

Gnomad4 SAS exome AF: 0.000105

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000680

Gnomad4 OTH exome AF: 0.0000176

GnomAD4 genome AF: 0.000430 AC: 8 AN: 18612 Hom.: 0 Cov.: 25 AF XY: 0.000439 AC XY: 4 AN XY: 9102

Gnomad4 AFR AF: 0.000312

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00420

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00147

Gnomad4 NFE AF: 0.000595

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Bethlem myopathy 2;C4225314:Ullrich congenital muscular dystrophy 2 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Oct 08, 2023

- -

Computational scores

Source: dbNSFP v4.3

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

LitVar

Other links and lift over

dbSNP: rs752652515; hg19: chr6-75890932;