17-50184475-CAAAAAAA-CAAAAAAAAA

Variant names:

• chr17-50184475-C-CAA
• rs58879635
• NM_000088.4:c.*1025_*1026dupTT

Variant summary

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

The NM_000088.4(COL1A1):​c.*1025_*1026dupTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00477 in 121,444 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 0.00078 (1 hom., cov: 26)
  • Exomes 𝑓: 0.011 (0 hom.)
• Consequence: COL1A1 NM_000088.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.156

Genes affected

COL1A1 (HGNC:2197): (collagen type I alpha 1 chain) This gene encodes the pro-alpha1 chains of type I collagen whose triple helix comprises two alpha1 chains and one alpha2 chain. Type I is a fibril-forming collagen found in most connective tissues and is abundant in bone, cornea, dermis and tendon. Mutations in this gene are associated with osteogenesis imperfecta types I-IV, Ehlers-Danlos syndrome type VIIA, Ehlers-Danlos syndrome Classical type, Caffey Disease and idiopathic osteoporosis. Reciprocal translocations between chromosomes 17 and 22, where this gene and the gene for platelet-derived growth factor beta are located, are associated with a particular type of skin tumor called dermatofibrosarcoma protuberans, resulting from unregulated expression of the growth factor. Two transcripts, resulting from the use of alternate polyadenylation signals, have been identified for this gene. [provided by R. Dalgleish, Feb 2008]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.0108 (522/48364) while in subpopulation AFR AF= 0.0175 (38/2168). AF 95% confidence interval is 0.0131. There are 0 homozygotes in gnomad4_exome. There are 247 alleles in male gnomad4_exome subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 57 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL1A1	NM_000088.4	c.*1025_*1026dupTT		3_prime_UTR_variant	Exon 51 of 51	ENST00000225964.10	NP_000079.2
COL1A1	XM_011524341.2	c.*1025_*1026dupTT		3_prime_UTR_variant	Exon 48 of 48		XP_011522643.1
COL1A1	XM_005257058.5	c.*1025_*1026dupTT		3_prime_UTR_variant	Exon 49 of 49		XP_005257115.2
COL1A1	XM_005257059.5	c.*1025_*1026dupTT		3_prime_UTR_variant	Exon 38 of 38		XP_005257116.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL1A1	ENST00000225964	c.*1025_*1026dupTT		3_prime_UTR_variant	Exon 51 of 51	1	NM_000088.4	ENSP00000225964.6

Frequencies

GnomAD3 genomes AF: 0.000780 AC: 57 AN: 73080 Hom.: 1 Cov.: 26

Gnomad AFR AF: 0.00181

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000319

Gnomad ASJ AF: 0.00176

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000925

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000320

Gnomad OTH AF: 0.00112

GnomAD4 exome AF: 0.0108 AC: 522 AN: 48364 Hom.: 0 Cov.: 0 AF XY: 0.0110 AC XY: 247 AN XY: 22440

Gnomad4 AFR exome AF: 0.0175

Gnomad4 AMR exome AF: 0.00759

Gnomad4 ASJ exome AF: 0.00903

Gnomad4 EAS exome AF: 0.00578

Gnomad4 SAS exome AF: 0.00926

Gnomad4 FIN exome AF: 0.0156

Gnomad4 NFE exome AF: 0.0116

Gnomad4 OTH exome AF: 0.0136

GnomAD4 genome AF: 0.000780 AC: 57 AN: 73080 Hom.: 1 Cov.: 26 AF XY: 0.000979 AC XY: 34 AN XY: 34744

Gnomad4 AFR AF: 0.00181

Gnomad4 AMR AF: 0.000319

Gnomad4 ASJ AF: 0.00176

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000927

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000320

Gnomad4 OTH AF: 0.00111

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs58879635; hg19: chr17-48261836;