NM_000093.5:c.2646+412G>T

Variant names:

• chr9-134786460-G-T
• rs3128621
• NM_000093.5:c.2646+412G>T

Variant summary

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

The NM_000093.5(COL5A1):​c.2646+412G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.369 in 152,046 control chromosomes in the GnomAD database, including 12,156 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 0.37 (12156 hom., cov: 32)
• Consequence: COL5A1 NM_000093.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.598

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.482 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL5A1	NM_000093.5	c.2646+412G>T		intron_variant	Intron 31 of 65	ENST00000371817.8	NP_000084.3
COL5A1	NM_001278074.1	c.2646+412G>T		intron_variant	Intron 31 of 65		NP_001265003.1
COL5A1	XM_017014266.3	c.2646+412G>T		intron_variant	Intron 31 of 64		XP_016869755.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL5A1	ENST00000371817.8	c.2646+412G>T		intron_variant	Intron 31 of 65	1	NM_000093.5	ENSP00000360882.3
COL5A1	ENST00000371820.4	c.2646+412G>T		intron_variant	Intron 31 of 65	2		ENSP00000360885.4

Frequencies

GnomAD3 genomes AF: 0.369 AC: 56042 AN: 151928 Hom.: 12153 Cov.: 32

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.662

Gnomad AMR AF: 0.492

Gnomad ASJ AF: 0.493

Gnomad EAS AF: 0.154

Gnomad SAS AF: 0.467

Gnomad FIN AF: 0.468

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.461

Gnomad OTH AF: 0.403

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

GnomAD4 genome AF: 0.369 AC: 56044 AN: 152046 Hom.: 12156 Cov.: 32 AF XY: 0.372 AC XY: 27648 AN XY: 74302

Gnomad4 AFR AF: 0.142

Gnomad4 AMR AF: 0.492

Gnomad4 ASJ AF: 0.493

Gnomad4 EAS AF: 0.153

Gnomad4 SAS AF: 0.467

Gnomad4 FIN AF: 0.468

Gnomad4 NFE AF: 0.461

Gnomad4 OTH AF: 0.405

Alfa AF: 0.455 Hom.: 21593

Bravo AF: 0.360

Asia WGS AF: 0.314 AC: 1092 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.56
DANN	Benign	0.60

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: rs3128621; hg19: chr9-137678306;