6-75086337-A-C

Position:

• chr6-75086337-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004370.6(COL12A1):​c.*210T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.016 in 330,192 control chromosomes in the GnomAD database, including 249 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.030 (223 hom., cov: 32)
  • Exomes 𝑓: 0.0037 (26 hom.)
• Consequence: COL12A1 NM_004370.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.02

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 6-75086337-A-C is Benign according to our data. Variant chr6-75086337-A-C is described in ClinVar as [Benign]. Clinvar id is 1289475.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL12A1	NM_004370.6	c.*210T>G		3_prime_UTR_variant	66/66	ENST00000322507.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL12A1	ENST00000322507.13	c.*210T>G		3_prime_UTR_variant	66/66	1	NM_004370.6	P4
COL12A1	ENST00000425443.6	c.2096-972T>G		intron_variant		5
COL12A1	ENST00000680981.1	n.811T>G		non_coding_transcript_exon_variant	4/4
COL12A1	ENST00000681086.1	n.1185T>G		non_coding_transcript_exon_variant	2/2

Frequencies

GnomAD3 genomes AF: 0.0303 AC: 4615 AN: 152140 Hom.: 220 Cov.: 32

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0147

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000647

Gnomad OTH AF: 0.0244

GnomAD4 exome AF: 0.00372 AC: 662 AN: 177934 Hom.: 26 Cov.: 4 AF XY: 0.00313 AC XY: 295 AN XY: 94344

Gnomad4 AFR exome AF: 0.0988

Gnomad4 AMR exome AF: 0.00776

Gnomad4 ASJ exome AF: 0.00185

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000473

Gnomad4 OTH exome AF: 0.00853

GnomAD4 genome AF: 0.0304 AC: 4629 AN: 152258 Hom.: 223 Cov.: 32 AF XY: 0.0290 AC XY: 2160 AN XY: 74462

Gnomad4 AFR AF: 0.104

Gnomad4 AMR AF: 0.0146

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000632

Gnomad4 OTH AF: 0.0241

Alfa AF: 0.0228 Hom.: 18

Bravo AF: 0.0347

Asia WGS AF: 0.00433 AC: 15 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 03, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	13
DANN	Benign	0.87

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: rs80299357; hg19: chr6-75796053;