rs141102808

chr6-75113758-CAAAAG-C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_004370.6(COL12A1):c.7698-19_7698-15del variant causes a splice polypyrimidine tract, intron change. The variant allele was found at a frequency of 0.0141 in 1,500,544 control chromosomes in the GnomAD database, including 165 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.011 (10 hom., cov: 32)
  • Exomes 𝑓: 0.014 (155 hom.)
• Consequence: COL12A1 NM_004370.6 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 3.65

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 Benign. Variant got -16 ACMG points.

• BP6: Variant 6-75113758-CAAAAG-C is Benign according to our data. Variant chr6-75113758-CAAAAG-C is described in ClinVar as [Likely_benign]. Clinvar id is 259346.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-75113758-CAAAAG-C is described in Lovd as [Likely_benign]. Variant chr6-75113758-CAAAAG-C is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0111 (1560/140206) while in subpopulation NFE AF= 0.0183 (1148/62890). AF 95% confidence interval is 0.0174. There are 10 homozygotes in gnomad4. There are 759 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 10 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL12A1	NM_004370.6	c.7698-19_7698-15del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000322507.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL12A1	ENST00000322507.13	c.7698-19_7698-15del		splice_polypyrimidine_tract_variant, intron_variant		1	NM_004370.6	P4

Frequencies

GnomAD3 genomes AF: 0.0111 AC: 1560 AN: 140082 Hom.: 10 Cov.: 32

Gnomad AFR AF: 0.00272

Gnomad AMI AF: 0.00239

Gnomad AMR AF: 0.00656

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00188

Gnomad FIN AF: 0.0185

Gnomad MID AF: 0.00355

Gnomad NFE AF: 0.0183

Gnomad OTH AF: 0.0117

GnomAD3 exomes AF: 0.0107 AC: 2214 AN: 206878 Hom.: 14 AF XY: 0.0108 AC XY: 1222 AN XY: 113652

Gnomad AFR exome AF: 0.00262

Gnomad AMR exome AF: 0.00481

Gnomad ASJ exome AF: 0.000390

Gnomad EAS exome AF: 0.0000693

Gnomad SAS exome AF: 0.00176

Gnomad FIN exome AF: 0.0174

Gnomad NFE exome AF: 0.0165

Gnomad OTH exome AF: 0.0134

GnomAD4 exome AF: 0.0145 AC: 19657 AN: 1360338 Hom.: 155 AF XY: 0.0141 AC XY: 9538 AN XY: 674160

Gnomad4 AFR exome AF: 0.00174

Gnomad4 AMR exome AF: 0.00462

Gnomad4 ASJ exome AF: 0.000441

Gnomad4 EAS exome AF: 0.0000267

Gnomad4 SAS exome AF: 0.00209

Gnomad4 FIN exome AF: 0.0196

Gnomad4 NFE exome AF: 0.0167

Gnomad4 OTH exome AF: 0.0123

GnomAD4 genome AF: 0.0111 AC: 1560 AN: 140206 Hom.: 10 Cov.: 32 AF XY: 0.0111 AC XY: 759 AN XY: 68518

Gnomad4 AFR AF: 0.00271

Gnomad4 AMR AF: 0.00655

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00189

Gnomad4 FIN AF: 0.0185

Gnomad4 NFE AF: 0.0183

Gnomad4 OTH AF: 0.0116

Alfa AF: 0.0137 Hom.: 2

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 22, 2019	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

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

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs141102808; hg19: chr6-75823474;