Variant chr17-50184472-CCA-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BS1_SupportingBS2

The NM_000088.4(COL1A1):c.*1028_*1029del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00106 in 196,578 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00053 ( 0 hom., cov: 25)

Exomes 𝑓: 0.0020 ( 0 hom. )

Consequence

COL1A1
NM_000088.4 3_prime_UTR

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:3

Conservation

PhyloP100: 1.08

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]

COL1A1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000527 (66/125252) while in subpopulation EAS AF= 0.00801 (39/4870). AF 95% confidence interval is 0.00602. There are 0 homozygotes in gnomad4. There are 31 alleles in male gnomad4 subpopulation. Median coverage is 25. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High AC in GnomAd4 at 66 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
COL1A1	NM_000088.4 linkuse as main transcript	c.1028_1029del	3_prime_UTR_variant	51/51	ENST00000225964.10	NP_000079.2
COL1A1	XM_005257058.5 linkuse as main transcript	c.1028_1029del	3_prime_UTR_variant	49/49		XP_005257115.2
COL1A1	XM_005257059.5 linkuse as main transcript	c.1028_1029del	3_prime_UTR_variant	38/38		XP_005257116.2
COL1A1	XM_011524341.2 linkuse as main transcript	c.1028_1029del	3_prime_UTR_variant	48/48		XP_011522643.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL1A1	ENST00000225964.10 linkuse as main transcript	c.1028_1029del		3_prime_UTR_variant	51/51	1	NM_000088.4	ENSP00000225964	P1

Frequencies

GnomAD3 genomes

AF:

0.000519

AC:

AN:

125196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000608

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000245

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00778

Gnomad SAS

AF:

0.000246

Gnomad FIN

AF:

0.000270

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000311

Gnomad OTH

AF:

0.000578

GnomAD4 exome

AF:

0.00200

AC:

143

AN:

71326

Hom.:

AF XY:

0.00204

AC XY:

AN XY:

32906

show subpopulations

Gnomad4 AFR exome

AF:

0.000296

Gnomad4 AMR exome

AF:

0.00664

Gnomad4 ASJ exome

AF:

0.00156

Gnomad4 EAS exome

AF:

0.00207

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00543

Gnomad4 NFE exome

AF:

0.00186

Gnomad4 OTH exome

AF:

0.00289

GnomAD4 genome

AF:

0.000527

AC:

AN:

125252

Hom.:

Cov.:

AF XY:

0.000512

AC XY:

AN XY:

60520

show subpopulations

Gnomad4 AFR

AF:

0.0000607

Gnomad4 AMR

AF:

0.000245

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00801

Gnomad4 SAS

AF:

0.000246

Gnomad4 FIN

AF:

0.000270

Gnomad4 NFE

AF:

0.000311

Gnomad4 OTH

AF:

0.000573

Alfa

AF:

0.0000619

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:3

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Ehlers-Danlos syndrome type 7A

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Osteogenesis Imperfecta, Dominant

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Infantile cortical hyperostosis

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over