17-50196930-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000088.4(COL1A1):​c.804+80A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.841 in 1,518,086 control chromosomes in the GnomAD database, including 540,505 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.81 ( 50021 hom., cov: 32)
Exomes 𝑓: 0.84 ( 490484 hom. )

Consequence

COL1A1
NM_000088.4 intron

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.102
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 Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BP6
Variant 17-50196930-T-G is Benign according to our data. Variant chr17-50196930-T-G is described in ClinVar as [Benign]. Clinvar id is 674977.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.859 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
COL1A1NM_000088.4 linkuse as main transcriptc.804+80A>C intron_variant ENST00000225964.10 NP_000079.2 P02452
COL1A1XM_011524341.2 linkuse as main transcriptc.804+80A>C intron_variant XP_011522643.1
COL1A1XM_005257058.5 linkuse as main transcriptc.804+80A>C intron_variant XP_005257115.2
COL1A1XM_005257059.5 linkuse as main transcriptc.804+80A>C intron_variant XP_005257116.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
COL1A1ENST00000225964.10 linkuse as main transcriptc.804+80A>C intron_variant 1 NM_000088.4 ENSP00000225964.6 P02452
COL1A1ENST00000495677.1 linkuse as main transcriptn.531+80A>C intron_variant 3

Frequencies

GnomAD3 genomes
AF:
0.808
AC:
122816
AN:
152030
Hom.:
49997
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.733
Gnomad AMI
AF:
0.913
Gnomad AMR
AF:
0.750
Gnomad ASJ
AF:
0.856
Gnomad EAS
AF:
0.671
Gnomad SAS
AF:
0.737
Gnomad FIN
AF:
0.890
Gnomad MID
AF:
0.829
Gnomad NFE
AF:
0.865
Gnomad OTH
AF:
0.802
GnomAD4 exome
AF:
0.845
AC:
1154166
AN:
1365938
Hom.:
490484
AF XY:
0.842
AC XY:
576315
AN XY:
684520
show subpopulations
Gnomad4 AFR exome
AF:
0.733
Gnomad4 AMR exome
AF:
0.710
Gnomad4 ASJ exome
AF:
0.851
Gnomad4 EAS exome
AF:
0.631
Gnomad4 SAS exome
AF:
0.734
Gnomad4 FIN exome
AF:
0.876
Gnomad4 NFE exome
AF:
0.870
Gnomad4 OTH exome
AF:
0.837
GnomAD4 genome
AF:
0.808
AC:
122892
AN:
152148
Hom.:
50021
Cov.:
32
AF XY:
0.804
AC XY:
59825
AN XY:
74374
show subpopulations
Gnomad4 AFR
AF:
0.733
Gnomad4 AMR
AF:
0.750
Gnomad4 ASJ
AF:
0.856
Gnomad4 EAS
AF:
0.671
Gnomad4 SAS
AF:
0.738
Gnomad4 FIN
AF:
0.890
Gnomad4 NFE
AF:
0.865
Gnomad4 OTH
AF:
0.800
Alfa
AF:
0.836
Hom.:
24410
Bravo
AF:
0.793
Asia WGS
AF:
0.690
AC:
2401
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingGeneDxJun 14, 2018This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.89
CADD
Benign
9.1
DANN
Benign
0.46

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs2075555; hg19: chr17-48274291; COSMIC: COSV56809284; COSMIC: COSV56809284; API