chr9-134641824-G-T

Variant names:

• chr9-134641824-G-T
• rs780212970
• NM_000093.5:c.-364G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000093.5(COL5A1):​c.-364G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000425 in 235,396 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 34)
  • Exomes 𝑓: 0.0000042 (0 hom.)
• Consequence: COL5A1 NM_000093.5 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.10

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL5A1	NM_000093.5	c.-364G>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 66	ENST00000371817.8	NP_000084.3
COL5A1	NM_000093.5	c.-364G>T		5_prime_UTR_variant	Exon 1 of 66	ENST00000371817.8	NP_000084.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL5A1	ENST00000371817	c.-364G>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 66	1	NM_000093.5	ENSP00000360882.3
COL5A1	ENST00000371817	c.-364G>T		5_prime_UTR_variant	Exon 1 of 66	1	NM_000093.5	ENSP00000360882.3
COL5A1	ENST00000371820	c.-364G>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 66	2		ENSP00000360885.4
COL5A1	ENST00000371820	c.-364G>T		5_prime_UTR_variant	Exon 1 of 66	2		ENSP00000360885.4

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000425 AC: 1 AN: 235396 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 119630

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000445

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	19
DANN	Benign	0.97

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: rs780212970; hg19: chr9-137533670;