10-69802014-G-A

Position:

• chr10-69802014-G-A

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.-410G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.933 in 170,020 control chromosomes in the GnomAD database, including 74,402 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.93 (66122 hom., cov: 32)
  • Exomes 𝑓: 0.96 (8280 hom.)
• Consequence: COL13A1 NM_001368882.1 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0440

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 10-69802014-G-A is Benign according to our data. Variant chr10-69802014-G-A is described in ClinVar as [Benign]. Clinvar id is 1269754.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.978 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL13A1	NM_001368882.1	c.-410G>A		5_prime_UTR_variant	1/41	ENST00000645393.2	NP_001355811.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL13A1	ENST00000645393.2	c.-410G>A		5_prime_UTR_variant	1/41		NM_001368882.1	ENSP00000496051	P1

Frequencies

GnomAD3 genomes AF: 0.930 AC: 141401 AN: 152100 Hom.: 66074 Cov.: 32

Gnomad AFR AF: 0.836

Gnomad AMI AF: 0.964

Gnomad AMR AF: 0.959

Gnomad ASJ AF: 0.937

Gnomad EAS AF: 0.845

Gnomad SAS AF: 0.893

Gnomad FIN AF: 0.956

Gnomad MID AF: 0.940

Gnomad NFE AF: 0.984

Gnomad OTH AF: 0.934

GnomAD4 exome AF: 0.964 AC: 17153 AN: 17802 Hom.: 8280 Cov.: 0 AF XY: 0.965 AC XY: 8803 AN XY: 9122

Gnomad4 AFR exome AF: 0.826

Gnomad4 AMR exome AF: 0.969

Gnomad4 ASJ exome AF: 0.923

Gnomad4 EAS exome AF: 0.840

Gnomad4 SAS exome AF: 0.902

Gnomad4 FIN exome AF: 0.954

Gnomad4 NFE exome AF: 0.983

Gnomad4 OTH exome AF: 0.963

GnomAD4 genome AF: 0.930 AC: 141508 AN: 152218 Hom.: 66122 Cov.: 32 AF XY: 0.927 AC XY: 68958 AN XY: 74412

Gnomad4 AFR AF: 0.836

Gnomad4 AMR AF: 0.959

Gnomad4 ASJ AF: 0.937

Gnomad4 EAS AF: 0.845

Gnomad4 SAS AF: 0.893

Gnomad4 FIN AF: 0.956

Gnomad4 NFE AF: 0.984

Gnomad4 OTH AF: 0.935

Alfa AF: 0.948 Hom.: 10335

Bravo AF: 0.928

Asia WGS AF: 0.874 AC: 3041 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	May 10, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.8
DANN	Benign	0.78

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: rs2704505; hg19: chr10-71561770;