rs7874142

Positions:

• chr9-134812936-G-A
• chr9-134812936-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000093.5(COL5A1):​c.3852+224G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.612 in 151,694 control chromosomes in the GnomAD database, including 29,580 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.61 (29580 hom., cov: 31)
• Consequence: COL5A1 NM_000093.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.67

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 9-134812936-G-A is Benign according to our data. Variant chr9-134812936-G-A is described in ClinVar as [Benign]. Clinvar id is 1290385.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.8 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL5A1	NM_000093.5	c.3852+224G>A		intron_variant		ENST00000371817.8
COL5A1	NM_001278074.1	c.3852+224G>A		intron_variant
COL5A1	XM_017014266.3	c.3852+224G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL5A1	ENST00000371817.8	c.3852+224G>A		intron_variant		1	NM_000093.5	P4
COL5A1	ENST00000371820.4	c.3852+224G>A		intron_variant		2		A2

Frequencies

GnomAD3 genomes AF: 0.611 AC: 92684 AN: 151574 Hom.: 29530 Cov.: 31

Gnomad AFR AF: 0.807

Gnomad AMI AF: 0.508

Gnomad AMR AF: 0.492

Gnomad ASJ AF: 0.515

Gnomad EAS AF: 0.496

Gnomad SAS AF: 0.450

Gnomad FIN AF: 0.517

Gnomad MID AF: 0.587

Gnomad NFE AF: 0.561

Gnomad OTH AF: 0.596

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

GnomAD4 genome AF: 0.612 AC: 92792 AN: 151694 Hom.: 29580 Cov.: 31 AF XY: 0.600 AC XY: 44497 AN XY: 74134

Gnomad4 AFR AF: 0.808

Gnomad4 AMR AF: 0.491

Gnomad4 ASJ AF: 0.515

Gnomad4 EAS AF: 0.496

Gnomad4 SAS AF: 0.449

Gnomad4 FIN AF: 0.517

Gnomad4 NFE AF: 0.561

Gnomad4 OTH AF: 0.597

Alfa AF: 0.560 Hom.: 46368

Bravo AF: 0.622

Asia WGS AF: 0.507 AC: 1766 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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	-0.95
CADD	Benign	0.17
DANN	Benign	0.26

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: rs7874142; hg19: chr9-137704782;