rs4096395

Variant names:

• chr10-69956753-C-T
• rs4096395
• NM_001368882.1:c.2146-251C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-69956753-C-T
• chr10-69956753-C-A
• chr10-69956753-C-G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, G2P
• presynaptic congenital myasthenic syndrome

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

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000298084 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL13A1	NM_001368882.1	MANE Select	c.2146-251C>T		intron	N/A	NP_001355811.1	A0A2R8YGI3
	COL13A1	NM_001130103.2		c.2113-251C>T		intron	N/A	NP_001123575.1	Q5TAT6-1
	COL13A1	NM_080801.4		c.2047-251C>T		intron	N/A	NP_542991.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL13A1	ENST00000645393.2	MANE Select	c.2146-251C>T		intron	N/A	ENSP00000496051.1	A0A2R8YGI3
	COL13A1	ENST00000398978.8	TSL:5	c.2113-251C>T		intron	N/A	ENSP00000381949.3	Q5TAT6-1
	COL13A1	ENST00000354547.7	TSL:5	c.2047-251C>T		intron	N/A	ENSP00000346553.3	Q5TAT6-2

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

African (AFR) AF: 0.0645 AC: 625 AN: 9688

American (AMR) AF: 0.306 AC: 4493 AN: 14696

Ashkenazi Jewish (ASJ) AF: 0.300 AC: 2601 AN: 8680

East Asian (EAS) AF: 0.274 AC: 6085 AN: 22218

South Asian (SAS) AF: 0.224 AC: 4906 AN: 21938

European-Finnish (FIN) AF: 0.221 AC: 3806 AN: 17222

Middle Eastern (MID) AF: 0.231 AC: 288 AN: 1248

European-Non Finnish (NFE) AF: 0.254 AC: 40853 AN: 160996

Other (OTH) AF: 0.240 AC: 3942 AN: 16402

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

African (AFR) AF: 0.0660 AC: 2740 AN: 41546

American (AMR) AF: 0.253 AC: 3868 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.299 AC: 1036 AN: 3468

East Asian (EAS) AF: 0.240 AC: 1244 AN: 5174

South Asian (SAS) AF: 0.220 AC: 1061 AN: 4822

European-Finnish (FIN) AF: 0.235 AC: 2489 AN: 10594

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.260 AC: 17646 AN: 67972

Other (OTH) AF: 0.225 AC: 475 AN: 2108

Alfa AF: 0.239 Hom.: 12691

Bravo AF: 0.202

Asia WGS AF: 0.219 AC: 758 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.6
DANN	Benign	0.61
PhyloP100		0.17
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs4096395;

hg19: chr10-71716509;