NM_000093.5:c.-261_-259delAGG

Variant names:

• chr9-134641909-TGGA-T
• rs886063671
• NM_000093.5:c.-261_-259delAGG

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_000093.5(COL5A1):​c.-261_-259delAGG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00169 in 352,120 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0017 (0 hom., cov: 34)
  • Exomes 𝑓: 0.0017 (1 hom.)
• Consequence: COL5A1 NM_000093.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.278

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 -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00167 (250/149874) while in subpopulation AFR AF= 0.00592 (241/40702). AF 95% confidence interval is 0.00531. There are 0 homozygotes in gnomad4. There are 111 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 250 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL5A1	NM_000093.5	c.-261_-259delAGG		5_prime_UTR_variant	Exon 1 of 66	ENST00000371817.8	NP_000084.3
COL5A1	NM_001278074.1	c.-261_-259delAGG		5_prime_UTR_variant	Exon 1 of 66		NP_001265003.1
COL5A1	XM_017014266.3	c.-261_-259delAGG		5_prime_UTR_variant	Exon 1 of 65		XP_016869755.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL5A1	ENST00000371817	c.-261_-259delAGG		5_prime_UTR_variant	Exon 1 of 66	1	NM_000093.5	ENSP00000360882.3
COL5A1	ENST00000371820	c.-261_-259delAGG		5_prime_UTR_variant	Exon 1 of 66	2		ENSP00000360885.4

Frequencies

GnomAD3 genomes AF: 0.00168 AC: 251 AN: 149756 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.00596

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000198

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000967

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000594

Gnomad OTH AF: 0.000485

GnomAD4 exome AF: 0.00171 AC: 345 AN: 202246 Hom.: 1 AF XY: 0.00177 AC XY: 182 AN XY: 103056

Gnomad4 AFR exome AF: 0.00540

Gnomad4 AMR exome AF: 0.00151

Gnomad4 ASJ exome AF: 0.00162

Gnomad4 EAS exome AF: 0.000680

Gnomad4 SAS exome AF: 0.000785

Gnomad4 FIN exome AF: 0.00171

Gnomad4 NFE exome AF: 0.00169

Gnomad4 OTH exome AF: 0.00218

GnomAD4 genome AF: 0.00167 AC: 250 AN: 149874 Hom.: 0 Cov.: 34 AF XY: 0.00152 AC XY: 111 AN XY: 73182

Gnomad4 AFR AF: 0.00592

Gnomad4 AMR AF: 0.000198

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000967

Gnomad4 NFE AF: 0.0000594

Gnomad4 OTH AF: 0.000480

Asia WGS AF: 0.00376 AC: 13 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs886063671; hg19: chr9-137533755;