rs150200872

Variant names:

• chr9-134728655-G-A
• rs150200872
• NM_000093.5:c.787-15G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-134728655-G-A
• chr9-134728655-G-T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_000093.5(COL5A1):​c.787-15G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0152 in 1,613,746 control chromosomes in the GnomAD database, including 776 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.011 (53 hom., cov: 33)
  • Exomes 𝑓: 0.016 (723 hom.)
• Consequence: COL5A1 NM_000093.5 intron
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:5
• Conservation: PhyloP100: -0.155

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]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 9-134728655-G-A is Benign according to our data. Variant chr9-134728655-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 136924.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=1, Benign=4}. Variant chr9-134728655-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.118 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL5A1	NM_000093.5	c.787-15G>A		intron_variant	Intron 5 of 65	ENST00000371817.8	NP_000084.3
COL5A1	NM_001278074.1	c.787-15G>A		intron_variant	Intron 5 of 65		NP_001265003.1
COL5A1	XM_017014266.3	c.787-15G>A		intron_variant	Intron 5 of 64		XP_016869755.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL5A1	ENST00000371817.8	c.787-15G>A		intron_variant	Intron 5 of 65	1	NM_000093.5	ENSP00000360882.3
COL5A1	ENST00000371820.4	c.787-15G>A		intron_variant	Intron 5 of 65	2		ENSP00000360885.4

Frequencies

GnomAD3 genomes AF: 0.0106 AC: 1614 AN: 152146 Hom.: 52 Cov.: 33

Gnomad AFR AF: 0.00198

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00314

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.00251

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.0105

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0106

Gnomad OTH AF: 0.00860

GnomAD2 exomes AF: 0.0209 AC: 5253 AN: 251144 AF XY: 0.0259

Gnomad AFR exome AF: 0.00191

Gnomad AMR exome AF: 0.00211

Gnomad ASJ exome AF: 0.00397

Gnomad EAS exome AF: 0.00310

Gnomad FIN exome AF: 0.0128

Gnomad NFE exome AF: 0.00957

Gnomad OTH exome AF: 0.0157

GnomAD4 exome AF: 0.0157 AC: 22941 AN: 1461482 Hom.: 723 Cov.: 34 AF XY: 0.0185 AC XY: 13451 AN XY: 727036

Gnomad4 AFR exome AF: 0.00155 AC: 52 AN: 33480

Gnomad4 AMR exome AF: 0.00206 AC: 92 AN: 44722

Gnomad4 ASJ exome AF: 0.00322 AC: 84 AN: 26126

Gnomad4 EAS exome AF: 0.00212 AC: 84 AN: 39698

Gnomad4 SAS exome AF: 0.113 AC: 9782 AN: 86248

Gnomad4 FIN exome AF: 0.0143 AC: 760 AN: 53096

Gnomad4 NFE exome AF: 0.00998 AC: 11093 AN: 1111952

Gnomad4 Remaining exome AF: 0.0157 AC: 949 AN: 60392

GnomAD4 genome AF: 0.0106 AC: 1615 AN: 152264 Hom.: 53 Cov.: 33 AF XY: 0.0120 AC XY: 892 AN XY: 74460

Gnomad4 AFR AF: 0.00197 AC: 0.00197381 AN: 0.00197381

Gnomad4 AMR AF: 0.00314 AC: 0.00313603 AN: 0.00313603

Gnomad4 ASJ AF: 0.00346 AC: 0.00345821 AN: 0.00345821

Gnomad4 EAS AF: 0.00251 AC: 0.00251353 AN: 0.00251353

Gnomad4 SAS AF: 0.126 AC: 0.126296 AN: 0.126296

Gnomad4 FIN AF: 0.0105 AC: 0.0104579 AN: 0.0104579

Gnomad4 NFE AF: 0.0106 AC: 0.0105854 AN: 0.0105854

Gnomad4 OTH AF: 0.00851 AC: 0.00851466 AN: 0.00851466

Alfa AF: 0.00767 Hom.: 2

Bravo AF: 0.00665

Asia WGS AF: 0.0580 AC: 201 AN: 3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:5

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not specified Benign:2

Nov 16, 2012

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. -

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Ehlers-Danlos syndrome, classic type Uncertain:1

Nov 01, 2016

Center for Human Genetics, Inc, Center for Human Genetics, Inc

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Ehlers-Danlos syndrome type 7A Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

Mar 15, 2017

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant summary: The COL5A1 c.787-15G>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. However, these predictions have yet to be confirmed by functional studies. This variant was found in 2755/121118 control chromosomes (144 homozygotes) at a frequency of 0.0227464, which is approximately 18197 times the estimated maximal expected allele frequency of a pathogenic COL5A1 variant (0.0000013), suggesting this variant is likely a benign polymorphism. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as likely benign/benign. Taken together, this variant is classified as benign. -

Ehlers-Danlos syndrome, classic type, 1 Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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	-0.90
CADD	Benign	6.2
DANN	Benign	0.52
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

Publications

LitVar

Other links and lift over

dbSNP: rs150200872; hg19: chr9-137620501; COSMIC: COSV65671645; COSMIC: COSV65671645;