chr9-134766762-A-G

Variant names:

• chr9-134766762-A-G
• rs4842157
• NM_000093.5:c.2134-238A>G

Variant summary

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

The ENST00000371817.8(COL5A1):​c.2134-238A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.377 in 151,982 control chromosomes in the GnomAD database, including 11,231 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.38 (11231 hom., cov: 32)
• Consequence: COL5A1 ENST00000371817.8 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.291
• Publications: 14 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 9-134766762-A-G is Benign according to our data. Variant chr9-134766762-A-G is described in ClinVar as Benign. ClinVar VariationId is 678461.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.646 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000371817.8. 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
	COL5A1	NM_000093.5	MANE Select	c.2134-238A>G		intron	N/A	NP_000084.3
	COL5A1	NM_001278074.1		c.2134-238A>G		intron	N/A	NP_001265003.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL5A1	ENST00000371817.8	TSL:1 MANE Select	c.2134-238A>G		intron	N/A	ENSP00000360882.3
	COL5A1	ENST00000371820.4	TSL:2	c.2134-238A>G		intron	N/A	ENSP00000360885.4

Frequencies

GnomAD3 genomes AF: 0.377 AC: 57200 AN: 151864 Hom.: 11218 Cov.: 32

Gnomad AFR AF: 0.432

Gnomad AMI AF: 0.186

Gnomad AMR AF: 0.346

Gnomad ASJ AF: 0.330

Gnomad EAS AF: 0.664

Gnomad SAS AF: 0.427

Gnomad FIN AF: 0.288

Gnomad MID AF: 0.312

Gnomad NFE AF: 0.344

Gnomad OTH AF: 0.367

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

GnomAD4 genome AF: 0.377 AC: 57256 AN: 151982 Hom.: 11231 Cov.: 32 AF XY: 0.377 AC XY: 27988 AN XY: 74290

African (AFR) AF: 0.432 AC: 17914 AN: 41444

American (AMR) AF: 0.346 AC: 5283 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.330 AC: 1147 AN: 3472

East Asian (EAS) AF: 0.665 AC: 3433 AN: 5162

South Asian (SAS) AF: 0.427 AC: 2050 AN: 4804

European-Finnish (FIN) AF: 0.288 AC: 3046 AN: 10564

Middle Eastern (MID) AF: 0.308 AC: 90 AN: 292

European-Non Finnish (NFE) AF: 0.344 AC: 23353 AN: 67942

Other (OTH) AF: 0.365 AC: 770 AN: 2112

Alfa AF: 0.356 Hom.: 23784

Bravo AF: 0.385

Asia WGS AF: 0.525 AC: 1826 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.7
DANN	Benign	0.22
PhyloP100		-0.29
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: rs4842157; hg19: chr9-137658608; COSMIC: COSV65664824;