rs4746015

Variant names:

• chr10-69953140-G-A
• rs4746015
• NM_001368882.1:c.2145+172G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001368882.1(COL13A1):​c.2145+172G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.398 in 152,116 control chromosomes in the GnomAD database, including 12,196 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.40 (12196 hom., cov: 33)
• Consequence: COL13A1 NM_001368882.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.31
• Publications: 9 publications found

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]

COL13A1 Gene-Disease associations (from GenCC):

• congenital myasthenic syndrome 19

  Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia, G2P, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• presynaptic congenital myasthenic syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• postsynaptic congenital myasthenic syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 10-69953140-G-A is Benign according to our data. Variant chr10-69953140-G-A is described in ClinVar as Benign. ClinVar VariationId is 1231086.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.452 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001368882.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL13A1	NM_001368882.1	MANE Select	c.2145+172G>A		intron	N/A	NP_001355811.1
	COL13A1	NM_001130103.2		c.2112+172G>A		intron	N/A	NP_001123575.1
	COL13A1	NM_080801.4		c.2046+172G>A		intron	N/A	NP_542991.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL13A1	ENST00000645393.2	MANE Select	c.2145+172G>A		intron	N/A	ENSP00000496051.1
	COL13A1	ENST00000398978.8	TSL:5	c.2112+172G>A		intron	N/A	ENSP00000381949.3
	COL13A1	ENST00000354547.7	TSL:5	c.2046+172G>A		intron	N/A	ENSP00000346553.3

Frequencies

GnomAD3 genomes AF: 0.398 AC: 60542 AN: 151998 Hom.: 12157 Cov.: 33

Gnomad AFR AF: 0.412

Gnomad AMI AF: 0.336

Gnomad AMR AF: 0.410

Gnomad ASJ AF: 0.367

Gnomad EAS AF: 0.452

Gnomad SAS AF: 0.468

Gnomad FIN AF: 0.285

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.397

Gnomad OTH AF: 0.422

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

GnomAD4 genome AF: 0.398 AC: 60618 AN: 152116 Hom.: 12196 Cov.: 33 AF XY: 0.397 AC XY: 29513 AN XY: 74354

African (AFR) AF: 0.413 AC: 17129 AN: 41492

American (AMR) AF: 0.410 AC: 6274 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.367 AC: 1273 AN: 3470

East Asian (EAS) AF: 0.450 AC: 2335 AN: 5184

South Asian (SAS) AF: 0.468 AC: 2254 AN: 4820

European-Finnish (FIN) AF: 0.285 AC: 3011 AN: 10564

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.397 AC: 27015 AN: 67972

Other (OTH) AF: 0.422 AC: 891 AN: 2112

Alfa AF: 0.405 Hom.: 23954

Bravo AF: 0.409

Asia WGS AF: 0.446 AC: 1549 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 10, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.12
DANN	Benign	0.66
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4746015; hg19: chr10-71712896; COSMIC: COSV62572667; COSMIC: COSV62572667;