chr9-134812212-T-A

Position:

• chr9-134812212-T-A

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.3691-237T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.623 in 152,086 control chromosomes in the GnomAD database, including 30,944 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.62 (30944 hom., cov: 32)
• Consequence: COL5A1 NM_000093.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0830

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=-0.85).
• BP6: Variant 9-134812212-T-A is Benign according to our data. Variant chr9-134812212-T-A is described in ClinVar as [Benign]. Clinvar id is 1244380.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.83 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL5A1	NM_000093.5	c.3691-237T>A		intron_variant		ENST00000371817.8	NP_000084.3
COL5A1	NM_001278074.1	c.3691-237T>A		intron_variant			NP_001265003.1
COL5A1	XM_017014266.3	c.3691-237T>A		intron_variant			XP_016869755.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL5A1	ENST00000371817.8	c.3691-237T>A		intron_variant		1	NM_000093.5	ENSP00000360882.3
COL5A1	ENST00000371820.4	c.3691-237T>A		intron_variant		2		ENSP00000360885.4

Frequencies

GnomAD3 genomes AF: 0.622 AC: 94592 AN: 151968 Hom.: 30891 Cov.: 32

Gnomad AFR AF: 0.837

Gnomad AMI AF: 0.510

Gnomad AMR AF: 0.498

Gnomad ASJ AF: 0.517

Gnomad EAS AF: 0.501

Gnomad SAS AF: 0.455

Gnomad FIN AF: 0.523

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.564

Gnomad OTH AF: 0.607

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.623 AC: 94701 AN: 152086 Hom.: 30944 Cov.: 32 AF XY: 0.612 AC XY: 45495 AN XY: 74332

Gnomad4 AFR AF: 0.837

Gnomad4 AMR AF: 0.498

Gnomad4 ASJ AF: 0.517

Gnomad4 EAS AF: 0.500

Gnomad4 SAS AF: 0.455

Gnomad4 FIN AF: 0.523

Gnomad4 NFE AF: 0.564

Gnomad4 OTH AF: 0.609

Alfa AF: 0.597 Hom.: 3337

Bravo AF: 0.633

Asia WGS AF: 0.520 AC: 1811 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 23, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.9
DANN	Benign	0.77

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: rs10745387; hg19: chr9-137704058;