6-75086648-GTA-G

Variant names:

• chr6-75086648-GTA-G
• rs61611291
• NM_004370.6:c.9182-93_9182-92delTA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_004370.6(COL12A1):​c.9182-93_9182-92delTA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.462 in 288,450 control chromosomes in the GnomAD database, including 30,511 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.61 (28524 hom., cov: 0)
  • Exomes 𝑓: 0.31 (1987 hom.)
• Consequence: COL12A1 NM_004370.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.00
• Publications: 0 publications found

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]

COL12A1 Gene-Disease associations (from GenCC):

• Bethlem myopathy 2

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet
• Bethlem myopathy 2

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Illumina, Genomics England PanelApp
• Ullrich congenital muscular dystrophy 2

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• Bethlem myopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Ullrich congenital muscular dystrophy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 6-75086648-GTA-G is Benign according to our data. Variant chr6-75086648-GTA-G is described in ClinVar as [Benign]. Clinvar id is 1252836.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.732 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL12A1	NM_004370.6	c.9182-93_9182-92delTA		intron_variant	Intron 65 of 65	ENST00000322507.13	NP_004361.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL12A1	ENST00000322507.13	c.9182-93_9182-92delTA		intron_variant	Intron 65 of 65	1	NM_004370.6	ENSP00000325146.8

Frequencies

GnomAD3 genomes AF: 0.615 AC: 87065 AN: 141572 Hom.: 28529 Cov.: 0

Gnomad AFR AF: 0.338

Gnomad AMI AF: 0.625

Gnomad AMR AF: 0.683

Gnomad ASJ AF: 0.795

Gnomad EAS AF: 0.612

Gnomad SAS AF: 0.725

Gnomad FIN AF: 0.678

Gnomad MID AF: 0.783

Gnomad NFE AF: 0.738

Gnomad OTH AF: 0.670

GnomAD4 exome AF: 0.315 AC: 46235 AN: 146882 Hom.: 1987 AF XY: 0.313 AC XY: 25592 AN XY: 81878

African (AFR) AF: 0.143 AC: 364 AN: 2542

American (AMR) AF: 0.154 AC: 993 AN: 6460

Ashkenazi Jewish (ASJ) AF: 0.314 AC: 1338 AN: 4264

East Asian (EAS) AF: 0.256 AC: 1474 AN: 5758

South Asian (SAS) AF: 0.162 AC: 2079 AN: 12794

European-Finnish (FIN) AF: 0.397 AC: 7565 AN: 19040

Middle Eastern (MID) AF: 0.313 AC: 170 AN: 544

European-Non Finnish (NFE) AF: 0.341 AC: 30377 AN: 88974

Other (OTH) AF: 0.288 AC: 1875 AN: 6506

GnomAD4 genome AF: 0.615 AC: 87056 AN: 141568 Hom.: 28524 Cov.: 0 AF XY: 0.615 AC XY: 42142 AN XY: 68530

African (AFR) AF: 0.338 AC: 13070 AN: 38618

American (AMR) AF: 0.683 AC: 9665 AN: 14150

Ashkenazi Jewish (ASJ) AF: 0.795 AC: 2674 AN: 3362

East Asian (EAS) AF: 0.613 AC: 2983 AN: 4870

South Asian (SAS) AF: 0.725 AC: 3189 AN: 4396

European-Finnish (FIN) AF: 0.678 AC: 5478 AN: 8076

Middle Eastern (MID) AF: 0.784 AC: 210 AN: 268

European-Non Finnish (NFE) AF: 0.737 AC: 47936 AN: 65002

Other (OTH) AF: 0.669 AC: 1291 AN: 1930

Alfa AF: 0.595 Hom.: 1017

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 08, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs61611291; hg19: chr6-75796364;