6-75087561-A-G

Position:

• chr6-75087561-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_004370.6(COL12A1):​c.9181+16T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,744 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: COL12A1 NM_004370.6 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.112

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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09130898).
• BP6: Variant 6-75087561-A-G is Benign according to our data. Variant chr6-75087561-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2032556.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.9181+16T>C		intron_variant		ENST00000322507.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL12A1	ENST00000322507.13	c.9181+16T>C		intron_variant		1	NM_004370.6	P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460744 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 726702

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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

Invitae

Sep 25, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.077	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	3.3
DANN	Uncertain	1.0
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.0080	N
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.091	T
MetaSVM	Benign	-0.55	T
MutationTaster	Benign	1.0	N;N;N;N
PROVEAN	Benign	1.2	N
REVEL	Benign	0.11
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0020	D
Vest4		0.15
MutPred		0.43		Gain of glycosylation at L3062 (P = 0.018);
MVP		0.14
ClinPred		0.091	T
GERP RS		1.5

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-75797277;