rs4842157

Positions:

• chr9-134766762-A-G

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.2134-238A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.377 in 151,982 control chromosomes in the GnomAD database, including 11,231 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.38 (11231 hom., cov: 32)
• Consequence: COL5A1 NM_000093.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.291

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=-0.9).
• BP6: Variant 9-134766762-A-G is Benign according to our data. Variant chr9-134766762-A-G is described in ClinVar as [Benign]. Clinvar id is 678461.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.646 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL5A1	NM_000093.5	c.2134-238A>G		intron_variant		ENST00000371817.8	NP_000084.3
COL5A1	NM_001278074.1	c.2134-238A>G		intron_variant			NP_001265003.1
COL5A1	XM_017014266.3	c.2134-238A>G		intron_variant			XP_016869755.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL5A1	ENST00000371817.8	c.2134-238A>G		intron_variant		1	NM_000093.5	ENSP00000360882	P4
COL5A1	ENST00000371820.4	c.2134-238A>G		intron_variant		2		ENSP00000360885	A2

Frequencies

GnomAD3 genomes AF: 0.377 AC: 57200 AN: 151864 Hom.: 11218 Cov.: 32

Gnomad AFR AF: 0.432

Gnomad AMI AF: 0.186

Gnomad AMR AF: 0.346

Gnomad ASJ AF: 0.330

Gnomad EAS AF: 0.664

Gnomad SAS AF: 0.427

Gnomad FIN AF: 0.288

Gnomad MID AF: 0.312

Gnomad NFE AF: 0.344

Gnomad OTH AF: 0.367

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

GnomAD4 genome AF: 0.377 AC: 57256 AN: 151982 Hom.: 11231 Cov.: 32 AF XY: 0.377 AC XY: 27988 AN XY: 74290

Gnomad4 AFR AF: 0.432

Gnomad4 AMR AF: 0.346

Gnomad4 ASJ AF: 0.330

Gnomad4 EAS AF: 0.665

Gnomad4 SAS AF: 0.427

Gnomad4 FIN AF: 0.288

Gnomad4 NFE AF: 0.344

Gnomad4 OTH AF: 0.365

Alfa AF: 0.348 Hom.: 13835

Bravo AF: 0.385

Asia WGS AF: 0.525 AC: 1826 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 14, 2018

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.7
DANN	Benign	0.22

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: rs4842157; hg19: chr9-137658608; COSMIC: COSV65664824;