rs41310213

Positions:

chr9-134782642-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000093.5(COL5A1):c.2431-25G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 1,611,960 control chromosomes in the GnomAD database, including 15,020 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 2341 hom., cov: 33)

Exomes 𝑓: 0.13 ( 12679 hom. )

Consequence

COL5A1
NM_000093.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.832

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=-0.98).

BP6

Variant 9-134782642-G-A is Benign according to our data. Variant chr9-134782642-G-A is described in ClinVar as [Benign]. Clinvar id is 255062.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-134782642-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.253 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
COL5A1	NM_000093.5 linkuse as main transcript	c.2431-25G>A	intron_variant	ENST00000371817.8	NP_000084.3
COL5A1	NM_001278074.1 linkuse as main transcript	c.2431-25G>A	intron_variant		NP_001265003.1
COL5A1	XM_017014266.3 linkuse as main transcript	c.2431-25G>A	intron_variant		XP_016869755.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL5A1	ENST00000371817.8 linkuse as main transcript	c.2431-25G>A		intron_variant		1	NM_000093.5	ENSP00000360882	P4	P20908-1
COL5A1	ENST00000371820.4 linkuse as main transcript	c.2431-25G>A		intron_variant		2		ENSP00000360885	A2	P20908-2

Frequencies

GnomAD3 genomes

AF:

0.162

AC:

24632

AN:

152046

Hom.:

2338

Cov.:

show subpopulations

Gnomad AFR

AF:

0.257

Gnomad AMI

AF:

0.0143

Gnomad AMR

AF:

0.0999

Gnomad ASJ

AF:

0.131

Gnomad EAS

AF:

0.154

Gnomad SAS

AF:

0.0729

Gnomad FIN

AF:

0.160

Gnomad MID

AF:

0.108

Gnomad NFE

AF:

0.129

Gnomad OTH

AF:

0.167

GnomAD3 exomes

AF:

0.130

AC:

32661

AN:

251096

Hom.:

2513

AF XY:

0.126

AC XY:

17152

AN XY:

135820

show subpopulations

Gnomad AFR exome

AF:

0.263

Gnomad AMR exome

AF:

0.0747

Gnomad ASJ exome

AF:

0.125

Gnomad EAS exome

AF:

0.166

Gnomad SAS exome

AF:

0.0782

Gnomad FIN exome

AF:

0.160

Gnomad NFE exome

AF:

0.131

Gnomad OTH exome

AF:

0.125

GnomAD4 exome

AF:

0.128

AC:

186228

AN:

1459796

Hom.:

12679

Cov.:

AF XY:

0.126

AC XY:

91468

AN XY:

726368

show subpopulations

Gnomad4 AFR exome

AF:

0.264

Gnomad4 AMR exome

AF:

0.0787

Gnomad4 ASJ exome

AF:

0.128

Gnomad4 EAS exome

AF:

0.138

Gnomad4 SAS exome

AF:

0.0774

Gnomad4 FIN exome

AF:

0.156

Gnomad4 NFE exome

AF:

0.127

Gnomad4 OTH exome

AF:

0.138

GnomAD4 genome

AF:

0.162

AC:

24655

AN:

152164

Hom.:

2341

Cov.:

AF XY:

0.159

AC XY:

11803

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.257

Gnomad4 AMR

AF:

0.0998

Gnomad4 ASJ

AF:

0.131

Gnomad4 EAS

AF:

0.155

Gnomad4 SAS

AF:

0.0726

Gnomad4 FIN

AF:

0.160

Gnomad4 NFE

AF:

0.129

Gnomad4 OTH

AF:

0.165

Alfa

AF:

0.141

Hom.:

304

Bravo

AF:

0.164

Asia WGS

AF:

0.135

AC:

472

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 26, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Mar 15, 2017	Variant summary: The COL5A1 c.2431-25G>A variant involves the alteration of a non-conserved intronic nucleotide. One in silico tool predicts a benign outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing while ESE finder predicts the loss of a SRp40 binding motif. However, these predictions have yet to be confirmed by functional studies. This variant was found in 16316/120916 control chromosomes (1295 homozygotes) at a frequency of 0.1349367, which is approximately 107949 times the estimated maximal expected allele frequency of a pathogenic COL5A1 variant (0.0000013), suggesting this variant is likely a benign polymorphism. In addition, one clinical diagnostic laboratory and one reputable database classified this variant as benign. Taken together, this variant is classified as benign. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Fibromuscular dysplasia, multifocal

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Mar 15, 2022

- -

Ehlers-Danlos syndrome, classic type, 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Mar 15, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

4.3

DANN

Benign

0.49

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