rs201266825

chr6-75181207-G-A

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS1

The NM_004370.6(COL12A1):c.1896C>T(p.Tyr632=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00023 in 1,497,786 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0015 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00017 (1 hom.)
• Consequence: COL12A1 NM_004370.6 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.00

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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 6-75181207-G-A is Benign according to our data. Variant chr6-75181207-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 542518.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00148 (110/74240) while in subpopulation AFR AF= 0.00436 (92/21110). AF 95% confidence interval is 0.00364. There are 0 homozygotes in gnomad4. There are 55 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL12A1	NM_004370.6	c.1896C>T	p.Tyr632=	synonymous_variant	11/66	ENST00000322507.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL12A1	ENST00000322507.13	c.1896C>T	p.Tyr632=	synonymous_variant	11/66	1	NM_004370.6	P4

Frequencies

GnomAD3 genomes AF: 0.00147 AC: 109 AN: 74140 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00433

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00227

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000753

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000821

Gnomad OTH AF: 0.00231

GnomAD3 exomes AF: 0.000250 AC: 48 AN: 191852 Hom.: 0 AF XY: 0.000245 AC XY: 26 AN XY: 106178

Gnomad AFR exome AF: 0.00233

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000489

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000548

Gnomad OTH exome AF: 0.000234

GnomAD4 exome AF: 0.000165 AC: 235 AN: 1423546 Hom.: 1 Cov.: 31 AF XY: 0.000146 AC XY: 103 AN XY: 707262

Gnomad4 AFR exome AF: 0.00270

Gnomad4 AMR exome AF: 0.000212

Gnomad4 ASJ exome AF: 0.0000403

Gnomad4 EAS exome AF: 0.0000254

Gnomad4 SAS exome AF: 0.000211

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000942

Gnomad4 OTH exome AF: 0.000324

GnomAD4 genome AF: 0.00148 AC: 110 AN: 74240 Hom.: 0 Cov.: 31 AF XY: 0.00156 AC XY: 55 AN XY: 35276

Gnomad4 AFR AF: 0.00436

Gnomad4 AMR AF: 0.00227

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000749

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000821

Gnomad4 OTH AF: 0.00228

Alfa AF: 0.000348 Hom.: 0

Bravo AF: 0.000820

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 14, 2020

- -

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

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
Cadd	Benign	0.83
Dann	Benign	0.13

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs201266825; hg19: chr6-75890923; COSMIC: COSV59392401;