rs773032514

Positions:

• chr9-134811483-T-TC

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_000093.5(COL5A1):​c.3583-6dupC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: COL5A1 NM_000093.5 splice_region, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.497

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 9-134811483-T-TC is Benign according to our data. Variant chr9-134811483-T-TC is described in ClinVar as [Likely_benign]. Clinvar id is 459679.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL5A1	NM_000093.5	c.3583-6dupC		splice_region_variant, intron_variant		ENST00000371817.8	NP_000084.3
COL5A1	NM_001278074.1	c.3583-6dupC		splice_region_variant, intron_variant			NP_001265003.1
COL5A1	XM_017014266.3	c.3583-6dupC		splice_region_variant, intron_variant			XP_016869755.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL5A1	ENST00000371817.8	c.3583-6dupC		splice_region_variant, intron_variant		1	NM_000093.5	ENSP00000360882.3
COL5A1	ENST00000371820.4	c.3583-6dupC		splice_region_variant, intron_variant		2		ENSP00000360885.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000403 AC: 1 AN: 248404 Hom.: 0 AF XY: 0.00000743 AC XY: 1 AN XY: 134580

Gnomad AFR exome AF: 0.0000627

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Ehlers-Danlos syndrome, classic type, 1 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Sep 07, 2018

- -

Computational scores

Source: dbNSFP v4.3

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: rs773032514; hg19: chr9-137703329;