17-50191660-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_000088.4(COL1A1):​c.2127+128G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000195 in 1,026,620 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: 0.0000019 ( 0 hom. )

Consequence

COL1A1
NM_000088.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.221
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
COL1A1NM_000088.4 linkuse as main transcriptc.2127+128G>A intron_variant ENST00000225964.10
COL1A1XM_005257058.5 linkuse as main transcriptc.2127+128G>A intron_variant
COL1A1XM_005257059.5 linkuse as main transcriptc.1209+128G>A intron_variant
COL1A1XM_011524341.2 linkuse as main transcriptc.1929+128G>A intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
COL1A1ENST00000225964.10 linkuse as main transcriptc.2127+128G>A intron_variant 1 NM_000088.4 P1
COL1A1ENST00000476387.1 linkuse as main transcriptn.476+128G>A intron_variant, non_coding_transcript_variant 2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000195
AC:
2
AN:
1026620
Hom.:
0
Cov.:
14
AF XY:
0.00000192
AC XY:
1
AN XY:
521170
show subpopulations
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000268
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
-0.81
CADD
Benign
8.9
DANN
Benign
0.61

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2075556; hg19: chr17-48269021; API