6-75087281-GAAA-GA

Variant names:

• chr6-75087281-GAA-G
• rs11289042
• NM_004370.6:c.9181+294_9181+295delTT

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS1

The NM_004370.6(COL12A1):​c.9181+294_9181+295delTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00229 in 303,424 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00023 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0043 (1 hom.)
• Consequence: COL12A1 NM_004370.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.554

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 -4 ACMG points.

• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000225 (34/150778) while in subpopulation SAS AF= 0.0021 (10/4762). AF 95% confidence interval is 0.00114. There are 0 homozygotes in gnomad4. There are 21 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL12A1	NM_004370.6	c.9181+294_9181+295delTT		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.9181+294_9181+295delTT		intron_variant	Intron 65 of 65	1	NM_004370.6	ENSP00000325146.8

Frequencies

GnomAD3 genomes AF: 0.000232 AC: 35 AN: 150674 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000390

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000198

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.00231

Gnomad FIN AF: 0.0000982

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000295

Gnomad OTH AF: 0.000483

GnomAD4 exome AF: 0.00433 AC: 661 AN: 152646 Hom.: 1 AF XY: 0.00483 AC XY: 373 AN XY: 77296

Gnomad4 AFR exome AF: 0.00243

Gnomad4 AMR exome AF: 0.00544

Gnomad4 ASJ exome AF: 0.00241

Gnomad4 EAS exome AF: 0.00471

Gnomad4 SAS exome AF: 0.0140

Gnomad4 FIN exome AF: 0.00506

Gnomad4 NFE exome AF: 0.00406

Gnomad4 OTH exome AF: 0.00413

GnomAD4 genome AF: 0.000225 AC: 34 AN: 150778 Hom.: 0 Cov.: 0 AF XY: 0.000285 AC XY: 21 AN XY: 73576

Gnomad4 AFR AF: 0.000389

Gnomad4 AMR AF: 0.000198

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.00210

Gnomad4 FIN AF: 0.0000982

Gnomad4 NFE AF: 0.0000296

Gnomad4 OTH AF: 0.000478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs11289042; hg19: chr6-75796997;