chr9-134691085-T-G

Position:

chr9-134691085-T-G

Variant summary

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

The NM_000093.5(COL5A1):c.277+6T>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000286 in 1,612,736 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0016 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00015 ( 1 hom. )

Consequence

COL5A1
NM_000093.5 splice_region, intron

Scores

Splicing: ADA: 0.0002037

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.0360

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:

COL5A1 (HGNC:):

COL5A1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 9-134691085-T-G is Benign according to our data. Variant chr9-134691085-T-G is described in ClinVar as [Benign]. Clinvar id is 283150.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00159 (243/152364) while in subpopulation AFR AF= 0.00546 (227/41594). AF 95% confidence interval is 0.00488. There are 0 homozygotes in gnomad4. There are 105 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 243 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
COL5A1	NM_000093.5 linkuse as main transcript	c.277+6T>G	splice_region_variant, intron_variant	ENST00000371817.8	NP_000084.3	P20908-1A0A024R8E5B2ZZ86Q59EE7
COL5A1	NM_001278074.1 linkuse as main transcript	c.277+6T>G	splice_region_variant, intron_variant		NP_001265003.1	B2ZZ86Q59EE7
COL5A1	XM_017014266.3 linkuse as main transcript	c.277+6T>G	splice_region_variant, intron_variant		XP_016869755.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
COL5A1	ENST00000371817.8 linkuse as main transcript	c.277+6T>G	splice_region_variant, intron_variant	1	NM_000093.5	ENSP00000360882.3	P20908-1
COL5A1	ENST00000371820.4 linkuse as main transcript	c.277+6T>G	splice_region_variant, intron_variant	2		ENSP00000360885.4	P20908-2H7BY82
COL5A1	ENST00000464187.1 linkuse as main transcript	n.463+6T>G	splice_region_variant, intron_variant	2

Frequencies

GnomAD3 genomes

AF:

0.00160

AC:

243

AN:

152246

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00547

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.000380

AC:

AN:

250018

Hom.:

AF XY:

0.000303

AC XY:

AN XY:

135420

show subpopulations

Gnomad AFR exome

AF:

0.00487

Gnomad AMR exome

AF:

0.000405

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:

0.000327

GnomAD4 exome

AF:

0.000150

AC:

219

AN:

1460372

Hom.:

Cov.:

AF XY:

0.000146

AC XY:

106

AN XY:

726522

show subpopulations

Gnomad4 AFR exome

AF:

0.00535

Gnomad4 AMR exome

AF:

0.000470

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.000282

GnomAD4 genome

AF:

0.00159

AC:

243

AN:

152364

Hom.:

Cov.:

AF XY:

0.00141

AC XY:

105

AN XY:

74506

show subpopulations

Gnomad4 AFR

AF:

0.00546

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.000803

Hom.:

Bravo

AF:

0.00181

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 15, 2017	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. -
Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Jul 21, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Sep 25, 2015	- -

Ehlers-Danlos syndrome, classic type, 1

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 25, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Mar 15, 2022	- -

Fibromuscular dysplasia, multifocal

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Mar 15, 2022

- -

COL5A1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 03, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

4.4

DANN

Benign

0.41

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00020

dbscSNV1_RF

Benign

0.032

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