chr9-134825764-T-G

Position:

• chr9-134825764-T-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The ENST00000371817.8(COL5A1):​c.4955-28T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000598 in 1,338,694 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: 33)
  • Exomes 𝑓: 0.0000060 (0 hom.)
• Consequence: COL5A1 ENST00000371817.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.28

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]

LOC101448202 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BS2: High AC in GnomAdExome4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL5A1	NM_000093.5	c.4955-28T>G		intron_variant		ENST00000371817.8	NP_000084.3
LOC101448202	NR_103451.2	n.71-5555A>C		intron_variant, non_coding_transcript_variant
COL5A1	NM_001278074.1	c.4955-28T>G		intron_variant			NP_001265003.1
COL5A1	XM_017014266.3	c.4955-28T>G		intron_variant			XP_016869755.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL5A1	ENST00000371817.8	c.4955-28T>G		intron_variant		1	NM_000093.5	ENSP00000360882	P4
COL5A1	ENST00000371820.4	c.4955-28T>G		intron_variant		2		ENSP00000360885	A2
COL5A1	ENST00000460264.5	n.423-28T>G		intron_variant, non_coding_transcript_variant		3
COL5A1	ENST00000465877.1	n.135-28T>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000598 AC: 8 AN: 1338694 Hom.: 0 Cov.: 18 AF XY: 0.00000446 AC XY: 3 AN XY: 672646

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: 0.0000360

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000499

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.040
DANN	Benign	0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.20		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.20		Position offset: 28

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7868111; hg19: chr9-137717610;