6-75181218-A-T

Position:

• chr6-75181218-A-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The ENST00000322507.13(COL12A1):​c.1892-7T>A 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 0.00000883 in 1,019,614 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.0000088 (0 hom.)
• Consequence: COL12A1 ENST00000322507.13 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.008907
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.687

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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 6-75181218-A-T is Benign according to our data. Variant chr6-75181218-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 836505.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL12A1	NM_004370.6	c.1892-7T>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000322507.13	NP_004361.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL12A1	ENST00000322507.13	c.1892-7T>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_004370.6	ENSP00000325146	P4

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD3 exomes AF: 0.00210 AC: 69 AN: 32846 Hom.: 33 AF XY: 0.00202 AC XY: 37 AN XY: 18304

Gnomad AFR exome AF: 0.00126

Gnomad AMR exome AF: 0.00255

Gnomad ASJ exome AF: 0.00144

Gnomad EAS exome AF: 0.00649

Gnomad SAS exome AF: 0.00105

Gnomad FIN exome AF: 0.00168

Gnomad NFE exome AF: 0.00188

Gnomad OTH exome AF: 0.00568

GnomAD4 exome AF: 0.00000883 AC: 9 AN: 1019614 Hom.: 0 Cov.: 30 AF XY: 0.0000119 AC XY: 6 AN XY: 502750

Gnomad4 AFR exome AF: 0.000228

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000225

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000498

Gnomad4 OTH exome AF: 0.0000244

GnomAD4 genome Cov.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

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

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.4
DANN	Benign	0.58

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0089
dbscSNV1_RF	Benign	0.078
SpliceAI score (max)		0.010		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: rs779185109; hg19: chr6-75890934;