rs112600748

Positions:

• chr9-134825924-C-G

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.5067+20C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00315 in 1,548,826 control chromosomes in the GnomAD database, including 116 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.016 (56 hom., cov: 34)
  • Exomes 𝑓: 0.0018 (60 hom.)
• Consequence: COL5A1 NM_000093.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -2.97

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]

LOC101448202 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BP6: Variant 9-134825924-C-G is Benign according to our data. Variant chr9-134825924-C-G is described in ClinVar as [Benign]. Clinvar id is 136907.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-134825924-C-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0522 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL5A1	NM_000093.5	c.5067+20C>G		intron_variant		ENST00000371817.8
LOC101448202	NR_103451.2	n.71-5715G>C		intron_variant, non_coding_transcript_variant
COL5A1	NM_001278074.1	c.5067+20C>G		intron_variant
COL5A1	XM_017014266.3	c.5067+20C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL5A1	ENST00000371817.8	c.5067+20C>G		intron_variant		1	NM_000093.5	P4
COL5A1	ENST00000371820.4	c.5067+20C>G		intron_variant		2		A2
COL5A1	ENST00000460264.5	n.535+20C>G		intron_variant, non_coding_transcript_variant		3
COL5A1	ENST00000465877.1	n.247+20C>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0156 AC: 2381 AN: 152234 Hom.: 55 Cov.: 34

Gnomad AFR AF: 0.0541

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00504

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000558

Gnomad OTH AF: 0.0105

GnomAD3 exomes AF: 0.00441 AC: 1106 AN: 250642 Hom.: 20 AF XY: 0.00310 AC XY: 420 AN XY: 135598

Gnomad AFR exome AF: 0.0549

Gnomad AMR exome AF: 0.00472

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000981

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000353

Gnomad OTH exome AF: 0.00213

GnomAD4 exome AF: 0.00179 AC: 2494 AN: 1396474 Hom.: 60 Cov.: 22 AF XY: 0.00153 AC XY: 1070 AN XY: 698310

Gnomad4 AFR exome AF: 0.0542

Gnomad4 AMR exome AF: 0.00503

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000826

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000231

Gnomad4 OTH exome AF: 0.00416

GnomAD4 genome AF: 0.0157 AC: 2389 AN: 152352 Hom.: 56 Cov.: 34 AF XY: 0.0146 AC XY: 1089 AN XY: 74494

Gnomad4 AFR AF: 0.0541

Gnomad4 AMR AF: 0.00503

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000558

Gnomad4 OTH AF: 0.0104

Alfa AF: 0.00735 Hom.: 5

Bravo AF: 0.0174

Asia WGS AF: 0.00404 AC: 14 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

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	GeneDx	Apr 15, 2013	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	PreventionGenetics, part of Exact Sciences	-	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Aug 11, 2023	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Ehlers-Danlos syndrome, classic type, 1 Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.072
DANN	Benign	0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs112600748; hg19: chr9-137717770;