9-134767390-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_000093.5(COL5A1):c.2232+36C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0255 in 1,598,972 control chromosomes in the GnomAD database, including 582 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.025 ( 46 hom., cov: 33)

Exomes 𝑓: 0.026 ( 536 hom. )

Consequence

COL5A1
NM_000093.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.0170

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 9-134767390-C-T is Benign according to our data. Variant chr9-134767390-C-T is described in ClinVar as [Benign]. Clinvar id is 255061.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0249 (3794/152258) while in subpopulation EAS AF= 0.0529 (273/5164). AF 95% confidence interval is 0.0477. There are 46 homozygotes in gnomad4. There are 1868 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 3794 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
COL5A1	NM_000093.5 link	c.2232+36C>T	intron_variant	Intron 24 of 65	ENST00000371817.8	NP_000084.3	P20908-1A0A024R8E5B2ZZ86Q59EE7
COL5A1	NM_001278074.1 link	c.2232+36C>T	intron_variant	Intron 24 of 65		NP_001265003.1	B2ZZ86Q59EE7
COL5A1	XM_017014266.3 link	c.2232+36C>T	intron_variant	Intron 24 of 64		XP_016869755.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL5A1	ENST00000371817.8 link	c.2232+36C>T		intron_variant	Intron 24 of 65	1	NM_000093.5	ENSP00000360882.3		P20908-1
COL5A1	ENST00000371820.4 link	c.2232+36C>T		intron_variant	Intron 24 of 65	2		ENSP00000360885.4		P20908-2H7BY82

Frequencies

GnomAD3 genomes

AF:

0.0249

AC:

3793

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0218

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0182

Gnomad ASJ

AF:

0.0182

Gnomad EAS

AF:

0.0529

Gnomad SAS

AF:

0.0236

Gnomad FIN

AF:

0.0321

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0258

Gnomad OTH

AF:

0.0292

GnomAD3 exomes

AF:

0.0264

AC:

6599

AN:

249828

Hom.:

106

AF XY:

0.0265

AC XY:

3583

AN XY:

135278

show subpopulations

Gnomad AFR exome

AF:

0.0235

Gnomad AMR exome

AF:

0.0186

Gnomad ASJ exome

AF:

0.0182

Gnomad EAS exome

AF:

0.0568

Gnomad SAS exome

AF:

0.0240

Gnomad FIN exome

AF:

0.0287

Gnomad NFE exome

AF:

0.0252

Gnomad OTH exome

AF:

0.0264

GnomAD4 exome

AF:

0.0256

AC:

36994

AN:

1446714

Hom.:

536

Cov.:

AF XY:

0.0256

AC XY:

18426

AN XY:

720464

show subpopulations

Gnomad4 AFR exome

AF:

0.0209

Gnomad4 AMR exome

AF:

0.0184

Gnomad4 ASJ exome

AF:

0.0195

Gnomad4 EAS exome

AF:

0.0399

Gnomad4 SAS exome

AF:

0.0244

Gnomad4 FIN exome

AF:

0.0294

Gnomad4 NFE exome

AF:

0.0254

Gnomad4 OTH exome

AF:

0.0286

GnomAD4 genome

AF:

0.0249

AC:

3794

AN:

152258

Hom.:

Cov.:

AF XY:

0.0251

AC XY:

1868

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.0218

Gnomad4 AMR

AF:

0.0181

Gnomad4 ASJ

AF:

0.0182

Gnomad4 EAS

AF:

0.0529

Gnomad4 SAS

AF:

0.0238

Gnomad4 FIN

AF:

0.0321

Gnomad4 NFE

AF:

0.0258

Gnomad4 OTH

AF:

0.0289

Alfa

AF:

0.0268

Hom.:

Bravo

AF:

0.0232

Asia WGS

AF:

0.0390

AC:

137

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 19, 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. -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Fibromuscular dysplasia, multifocal

Benign:1

Mar 15, 2022

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Ehlers-Danlos syndrome, classic type, 1

Benign:1

Mar 15, 2022

Genome-Nilou Lab

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

-0.89

CADD

Benign

2.3

DANN

Benign

0.37

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over