9-134753803-C-T

Variant names:

• chr9-134753803-C-T
• rs79679217
• NM_000093.5:c.1720-47C>T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000093.5(COL5A1):​c.1720-47C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 1,257,210 control chromosomes in the GnomAD database, including 24,323 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2158 hom., cov: 27)
  • Exomes 𝑓: 0.20 (22165 hom.)
• Consequence: COL5A1 NM_000093.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -4.96

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

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 9-134753803-C-T is Benign according to our data. Variant chr9-134753803-C-T is described in ClinVar as [Benign]. Clinvar id is 255055.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.347 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL5A1	NM_000093.5	c.1720-47C>T		intron_variant	Intron 14 of 65	ENST00000371817.8	NP_000084.3
COL5A1	NM_001278074.1	c.1720-47C>T		intron_variant	Intron 14 of 65		NP_001265003.1
COL5A1	XM_017014266.3	c.1720-47C>T		intron_variant	Intron 14 of 64		XP_016869755.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL5A1	ENST00000371817.8	c.1720-47C>T		intron_variant	Intron 14 of 65	1	NM_000093.5	ENSP00000360882.3
COL5A1	ENST00000371820.4	c.1720-47C>T		intron_variant	Intron 14 of 65	2		ENSP00000360885.4

Frequencies

GnomAD3 genomes AF: 0.163 AC: 23992 AN: 147366 Hom.: 2156 Cov.: 27

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.345

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.361

Gnomad SAS AF: 0.147

Gnomad FIN AF: 0.195

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.157

GnomAD3 exomes AF: 0.169 AC: 42032 AN: 248424 Hom.: 4035 AF XY: 0.170 AC XY: 22925 AN XY: 134710

Gnomad AFR exome AF: 0.113

Gnomad AMR exome AF: 0.0917

Gnomad ASJ exome AF: 0.109

Gnomad EAS exome AF: 0.359

Gnomad SAS exome AF: 0.139

Gnomad FIN exome AF: 0.184

Gnomad NFE exome AF: 0.182

Gnomad OTH exome AF: 0.158

GnomAD4 exome AF: 0.203 AC: 225242 AN: 1109724 Hom.: 22165 Cov.: 18 AF XY: 0.201 AC XY: 112944 AN XY: 561558

Gnomad4 AFR exome AF: 0.123

Gnomad4 AMR exome AF: 0.106

Gnomad4 ASJ exome AF: 0.136

Gnomad4 EAS exome AF: 0.429

Gnomad4 SAS exome AF: 0.147

Gnomad4 FIN exome AF: 0.227

Gnomad4 NFE exome AF: 0.207

Gnomad4 OTH exome AF: 0.204

GnomAD4 genome AF: 0.163 AC: 23983 AN: 147486 Hom.: 2158 Cov.: 27 AF XY: 0.163 AC XY: 11730 AN XY: 71812

Gnomad4 AFR AF: 0.110

Gnomad4 AMR AF: 0.126

Gnomad4 ASJ AF: 0.113

Gnomad4 EAS AF: 0.361

Gnomad4 SAS AF: 0.146

Gnomad4 FIN AF: 0.195

Gnomad4 NFE AF: 0.185

Gnomad4 OTH AF: 0.155

Alfa AF: 0.127 Hom.: 359

Bravo AF: 0.158

Asia WGS AF: 0.179 AC: 624 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 26, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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	-0.92
CADD	Benign	0.0010
DANN	Benign	0.51

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: rs79679217; hg19: chr9-137645649; COSMIC: COSV65670625;