rs10484915

Positions:

• chr6-75173349-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004370.6(COL12A1):​c.2710+1689A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.074 in 152,234 control chromosomes in the GnomAD database, including 709 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.074 (709 hom., cov: 32)
• Consequence: COL12A1 NM_004370.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.04

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL12A1	NM_004370.6	c.2710+1689A>G		intron_variant		ENST00000322507.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL12A1	ENST00000322507.13	c.2710+1689A>G		intron_variant		1	NM_004370.6	P4
COL12A1	ENST00000345356.10	c.74-20867A>G		intron_variant		1
COL12A1	ENST00000416123.6	c.2710+1689A>G		intron_variant		5
COL12A1	ENST00000483888.6	c.2710+1689A>G		intron_variant		5		A1

Frequencies

GnomAD3 genomes AF: 0.0736 AC: 11196 AN: 152116 Hom.: 690 Cov.: 32

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.0875

Gnomad ASJ AF: 0.0562

Gnomad EAS AF: 0.222

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.0282

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0251

Gnomad OTH AF: 0.0700

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0740 AC: 11262 AN: 152234 Hom.: 709 Cov.: 32 AF XY: 0.0760 AC XY: 5656 AN XY: 74440

Gnomad4 AFR AF: 0.140

Gnomad4 AMR AF: 0.0883

Gnomad4 ASJ AF: 0.0562

Gnomad4 EAS AF: 0.222

Gnomad4 SAS AF: 0.120

Gnomad4 FIN AF: 0.0282

Gnomad4 NFE AF: 0.0251

Gnomad4 OTH AF: 0.0683

Alfa AF: 0.0531 Hom.: 55

Bravo AF: 0.0814

Asia WGS AF: 0.164 AC: 570 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.054
DANN	Benign	0.45

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: rs10484915; hg19: chr6-75883065;