10-69956753-C-T

Position:

• chr10-69956753-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001368882.1(COL13A1):​c.2146-251C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 425,268 control chromosomes in the GnomAD database, including 12,751 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (3761 hom., cov: 33)
  • Exomes 𝑓: 0.25 (8990 hom.)
• Consequence: COL13A1 NM_001368882.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.168

Genes affected

COL13A1 (HGNC:2190): (collagen type XIII alpha 1 chain) This gene encodes the alpha chain of one of the nonfibrillar collagens. The function of this gene product is not known, however, it has been detected at low levels in all connective tissue-producing cells so it may serve a general function in connective tissues. Unlike most of the collagens, which are secreted into the extracellular matrix, collagen XIII contains a transmembrane domain and the protein has been localized to the plasma membrane. The transcripts for this gene undergo complex and extensive splicing involving at least eight exons. Like other collagens, collagen XIII is a trimer; it is not known whether this trimer is composed of one or more than one alpha chain isomer. A number of alternatively spliced transcript variants have been described, but the full length nature of some of them has not been determined. [provided by RefSeq, Jul 2008]

LOC107984242 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 10-69956753-C-T is Benign according to our data. Variant chr10-69956753-C-T is described in ClinVar as [Benign]. Clinvar id is 1250042.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.256 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL13A1	NM_001368882.1	c.2146-251C>T		intron_variant		ENST00000645393.2	NP_001355811.1
LOC107984242	XR_007062181.1	n.296G>A		non_coding_transcript_exon_variant	3/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL13A1	ENST00000645393.2	c.2146-251C>T		intron_variant			NM_001368882.1	ENSP00000496051	P1

Frequencies

GnomAD3 genomes AF: 0.202 AC: 30716 AN: 152060 Hom.: 3752 Cov.: 33

Gnomad AFR AF: 0.0660

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.252

Gnomad ASJ AF: 0.299

Gnomad EAS AF: 0.241

Gnomad SAS AF: 0.221

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.223

GnomAD4 exome AF: 0.248 AC: 67599 AN: 273088 Hom.: 8990 Cov.: 0 AF XY: 0.248 AC XY: 35158 AN XY: 141584

Gnomad4 AFR exome AF: 0.0645

Gnomad4 AMR exome AF: 0.306

Gnomad4 ASJ exome AF: 0.300

Gnomad4 EAS exome AF: 0.274

Gnomad4 SAS exome AF: 0.224

Gnomad4 FIN exome AF: 0.221

Gnomad4 NFE exome AF: 0.254

Gnomad4 OTH exome AF: 0.240

GnomAD4 genome AF: 0.202 AC: 30728 AN: 152180 Hom.: 3761 Cov.: 33 AF XY: 0.201 AC XY: 14978 AN XY: 74400

Gnomad4 AFR AF: 0.0660

Gnomad4 AMR AF: 0.253

Gnomad4 ASJ AF: 0.299

Gnomad4 EAS AF: 0.240

Gnomad4 SAS AF: 0.220

Gnomad4 FIN AF: 0.235

Gnomad4 NFE AF: 0.260

Gnomad4 OTH AF: 0.225

Alfa AF: 0.249 Hom.: 8256

Bravo AF: 0.202

Asia WGS AF: 0.219 AC: 758 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 18, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.6
DANN	Benign	0.61

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: rs4096395; hg19: chr10-71716509;