9-134795468-C-T

Variant names:

• chr9-134795468-C-T
• rs4842167
• NM_000093.5:c.2799+153C>T

Variant summary

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

The NM_000093.5(COL5A1):​c.2799+153C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.658 in 151,636 control chromosomes in the GnomAD database, including 33,957 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.66 (33957 hom., cov: 29)
• Consequence: COL5A1 NM_000093.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.205
• Publications: 6 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 9-134795468-C-T is Benign according to our data. Variant chr9-134795468-C-T is described in ClinVar as Benign. ClinVar VariationId is 672248.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.834 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL5A1	NM_000093.5	c.2799+153C>T		intron_variant	Intron 34 of 65	ENST00000371817.8	NP_000084.3
COL5A1	NM_001278074.1	c.2799+153C>T		intron_variant	Intron 34 of 65		NP_001265003.1
COL5A1	XM_017014266.3	c.2799+153C>T		intron_variant	Intron 34 of 64		XP_016869755.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL5A1	ENST00000371817.8	c.2799+153C>T		intron_variant	Intron 34 of 65	1	NM_000093.5	ENSP00000360882.3
COL5A1	ENST00000371820.4	c.2799+153C>T		intron_variant	Intron 34 of 65	2		ENSP00000360885.4

Frequencies

GnomAD3 genomes AF: 0.658 AC: 99628 AN: 151518 Hom.: 33914 Cov.: 29

Gnomad AFR AF: 0.841

Gnomad AMI AF: 0.331

Gnomad AMR AF: 0.546

Gnomad ASJ AF: 0.610

Gnomad EAS AF: 0.825

Gnomad SAS AF: 0.585

Gnomad FIN AF: 0.571

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.584

Gnomad OTH AF: 0.639

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

GnomAD4 genome AF: 0.658 AC: 99728 AN: 151636 Hom.: 33957 Cov.: 29 AF XY: 0.654 AC XY: 48444 AN XY: 74084

African (AFR) AF: 0.841 AC: 34799 AN: 41364

American (AMR) AF: 0.546 AC: 8325 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.610 AC: 2117 AN: 3468

East Asian (EAS) AF: 0.824 AC: 4198 AN: 5092

South Asian (SAS) AF: 0.584 AC: 2807 AN: 4810

European-Finnish (FIN) AF: 0.571 AC: 5980 AN: 10482

Middle Eastern (MID) AF: 0.656 AC: 193 AN: 294

European-Non Finnish (NFE) AF: 0.584 AC: 39665 AN: 67874

Other (OTH) AF: 0.638 AC: 1343 AN: 2104

Alfa AF: 0.607 Hom.: 108913

Bravo AF: 0.666

Asia WGS AF: 0.722 AC: 2509 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	7.3
DANN	Benign	0.74
PhyloP100		-0.20
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs4842167; hg19: chr9-137687314; COSMIC: COSV106062896;