9-134732515-C-G

Position:

• chr9-134732515-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000093.5(COL5A1):​c.1389+388C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.498 in 373,570 control chromosomes in the GnomAD database, including 48,622 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.46 (17414 hom., cov: 33)
  • Exomes 𝑓: 0.52 (31208 hom.)
• Consequence: COL5A1 NM_000093.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.770

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.625 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL5A1	NM_000093.5	c.1389+388C>G		intron_variant		ENST00000371817.8	NP_000084.3
COL5A1	NM_001278074.1	c.1389+388C>G		intron_variant			NP_001265003.1
COL5A1	XM_017014266.3	c.1389+388C>G		intron_variant			XP_016869755.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL5A1	ENST00000371817.8	c.1389+388C>G		intron_variant		1	NM_000093.5	ENSP00000360882.3
COL5A1	ENST00000371820.4	c.1389+388C>G		intron_variant		2		ENSP00000360885.4
COL5A1	ENST00000469093.1	n.516C>G		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes AF: 0.461 AC: 69977 AN: 151908 Hom.: 17396 Cov.: 33

Gnomad AFR AF: 0.275

Gnomad AMI AF: 0.412

Gnomad AMR AF: 0.621

Gnomad ASJ AF: 0.686

Gnomad EAS AF: 0.486

Gnomad SAS AF: 0.643

Gnomad FIN AF: 0.509

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.502

Gnomad OTH AF: 0.513

GnomAD4 exome AF: 0.524 AC: 116170 AN: 221544 Hom.: 31208 Cov.: 0 AF XY: 0.532 AC XY: 61527 AN XY: 115606

Gnomad4 AFR exome AF: 0.271

Gnomad4 AMR exome AF: 0.686

Gnomad4 ASJ exome AF: 0.694

Gnomad4 EAS exome AF: 0.477

Gnomad4 SAS exome AF: 0.629

Gnomad4 FIN exome AF: 0.511

Gnomad4 NFE exome AF: 0.502

Gnomad4 OTH exome AF: 0.522

GnomAD4 genome AF: 0.461 AC: 70026 AN: 152026 Hom.: 17414 Cov.: 33 AF XY: 0.469 AC XY: 34833 AN XY: 74284

Gnomad4 AFR AF: 0.275

Gnomad4 AMR AF: 0.622

Gnomad4 ASJ AF: 0.686

Gnomad4 EAS AF: 0.485

Gnomad4 SAS AF: 0.644

Gnomad4 FIN AF: 0.509

Gnomad4 NFE AF: 0.502

Gnomad4 OTH AF: 0.516

Alfa AF: 0.309 Hom.: 793

Bravo AF: 0.457

Asia WGS AF: 0.592 AC: 2054 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.1
DANN	Benign	0.48

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: rs3124311; hg19: chr9-137624361;