NM_000093.5:c.1720-47C>T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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 Gene-Disease associations (from GenCC):

• Ehlers-Danlos syndrome

  Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
• Ehlers-Danlos syndrome, classic type

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet, Ambry Genetics, PanelApp Australia, Genomics England PanelApp
• Ehlers-Danlos syndrome, classic type, 1

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• arterial disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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

GnomAD2 exomes AF: 0.169 AC: 42032 AN: 248424 AF XY: 0.170

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 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

African (AFR) AF: 0.123 AC: 3186 AN: 25908

American (AMR) AF: 0.106 AC: 4260 AN: 40314

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 2659 AN: 19582

East Asian (EAS) AF: 0.429 AC: 13504 AN: 31510

South Asian (SAS) AF: 0.147 AC: 11755 AN: 79854

European-Finnish (FIN) AF: 0.227 AC: 9608 AN: 42234

Middle Eastern (MID) AF: 0.170 AC: 661 AN: 3890

European-Non Finnish (NFE) AF: 0.207 AC: 170456 AN: 821496

Other (OTH) AF: 0.204 AC: 9153 AN: 44936

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

African (AFR) AF: 0.110 AC: 4452 AN: 40400

American (AMR) AF: 0.126 AC: 1864 AN: 14782

Ashkenazi Jewish (ASJ) AF: 0.113 AC: 388 AN: 3428

East Asian (EAS) AF: 0.361 AC: 1698 AN: 4702

South Asian (SAS) AF: 0.146 AC: 629 AN: 4294

European-Finnish (FIN) AF: 0.195 AC: 1912 AN: 9808

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.185 AC: 12368 AN: 66838

Other (OTH) AF: 0.155 AC: 316 AN: 2042

Alfa AF: 0.145 Hom.: 663

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
PhyloP100		-5.0
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

Other links and lift over

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