rs10745387

Variant names:

• chr9-134812212-T-A
• rs10745387
• NM_000093.5:c.3691-237T>A

Your query was ambiguous. Multiple possible variants found:

• chr9-134812212-T-A
• chr9-134812212-T-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000093.5(COL5A1):​c.3691-237T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.623 in 152,086 control chromosomes in the GnomAD database, including 30,944 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.62 (30944 hom., cov: 32)
• Consequence: COL5A1 NM_000093.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0830
• Publications: 4 publications found

Genes affected

COL5A1 (HGNC:2209): (collagen type V alpha 1 chain) This gene encodes an alpha chain for one of the low abundance fibrillar collagens. Fibrillar collagen molecules are trimers that can be composed of one or more types of alpha chains. Type V collagen is found in tissues containing type I collagen and appears to regulate the assembly of heterotypic fibers composed of both type I and type V collagen. This gene product is closely related to type XI collagen and it is possible that the collagen chains of types V and XI constitute a single collagen type with tissue-specific chain combinations. The encoded procollagen protein occurs commonly as the heterotrimer pro-alpha1(V)-pro-alpha1(V)-pro-alpha2(V). Mutations in this gene are associated with Ehlers-Danlos syndrome, types I and II. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, May 2013]

COL5A1 Gene-Disease associations (from GenCC):

• Ehlers-Danlos syndrome

  Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
• Ehlers-Danlos syndrome, classic type

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet, Ambry Genetics, PanelApp Australia, Genomics England PanelApp
• Ehlers-Danlos syndrome, classic type, 1

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• arterial disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 9-134812212-T-A is Benign according to our data. Variant chr9-134812212-T-A is described in ClinVar as Benign. ClinVar VariationId is 1244380.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.83 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL5A1	NM_000093.5	c.3691-237T>A		intron_variant	Intron 46 of 65	ENST00000371817.8	NP_000084.3
COL5A1	NM_001278074.1	c.3691-237T>A		intron_variant	Intron 46 of 65		NP_001265003.1
COL5A1	XM_017014266.3	c.3691-237T>A		intron_variant	Intron 46 of 64		XP_016869755.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL5A1	ENST00000371817.8	c.3691-237T>A		intron_variant	Intron 46 of 65	1	NM_000093.5	ENSP00000360882.3
COL5A1	ENST00000371820.4	c.3691-237T>A		intron_variant	Intron 46 of 65	2		ENSP00000360885.4

Frequencies

GnomAD3 genomes AF: 0.622 AC: 94592 AN: 151968 Hom.: 30891 Cov.: 32

Gnomad AFR AF: 0.837

Gnomad AMI AF: 0.510

Gnomad AMR AF: 0.498

Gnomad ASJ AF: 0.517

Gnomad EAS AF: 0.501

Gnomad SAS AF: 0.455

Gnomad FIN AF: 0.523

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.564

Gnomad OTH AF: 0.607

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

GnomAD4 genome AF: 0.623 AC: 94701 AN: 152086 Hom.: 30944 Cov.: 32 AF XY: 0.612 AC XY: 45495 AN XY: 74332

African (AFR) AF: 0.837 AC: 34744 AN: 41494

American (AMR) AF: 0.498 AC: 7611 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.517 AC: 1795 AN: 3472

East Asian (EAS) AF: 0.500 AC: 2584 AN: 5164

South Asian (SAS) AF: 0.455 AC: 2191 AN: 4816

European-Finnish (FIN) AF: 0.523 AC: 5525 AN: 10572

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.564 AC: 38322 AN: 67972

Other (OTH) AF: 0.609 AC: 1286 AN: 2112

Alfa AF: 0.597 Hom.: 3337

Bravo AF: 0.633

Asia WGS AF: 0.520 AC: 1811 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 23, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.9
DANN	Benign	0.77
PhyloP100		-0.083
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: rs10745387; hg19: chr9-137704058;