rs2277634

chr17-50187848-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_000088.4(COL1A1):c.3369+28C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00104 in 1,552,920 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00079 (5 hom., cov: 33)
  • Exomes 𝑓: 0.0011 (30 hom.)
• Consequence: COL1A1 NM_000088.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.878

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 17-50187848-G-A is Benign according to our data. Variant chr17-50187848-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1189140.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000788 (120/152302) while in subpopulation EAS AF= 0.0226 (117/5178). AF 95% confidence interval is 0.0193. There are 5 homozygotes in gnomad4. There are 74 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd at 121 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL1A1	NM_000088.4	c.3369+28C>T		intron_variant		ENST00000225964.10
COL1A1	XM_005257058.5	c.3099+28C>T		intron_variant
COL1A1	XM_005257059.5	c.2451+28C>T		intron_variant
COL1A1	XM_011524341.2	c.3171+28C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL1A1	ENST00000225964.10	c.3369+28C>T		intron_variant		1	NM_000088.4	P1
COL1A1	ENST00000486572.1	n.595C>T		non_coding_transcript_exon_variant	2/2	3
COL1A1	ENST00000511732.1			downstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.000795 AC: 121 AN: 152184 Hom.: 5 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0227

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.00154 AC: 333 AN: 216436 Hom.: 5 AF XY: 0.00141 AC XY: 163 AN XY: 115684

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0179

Gnomad SAS exome AF: 0.0000854

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000821

Gnomad OTH exome AF: 0.000384

GnomAD4 exome AF: 0.00107 AC: 1497 AN: 1400618 Hom.: 30 Cov.: 29 AF XY: 0.00101 AC XY: 700 AN XY: 693908

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0361

Gnomad4 SAS exome AF: 0.0000634

Gnomad4 FIN exome AF: 0.0000197

Gnomad4 NFE exome AF: 0.0000373

Gnomad4 OTH exome AF: 0.000535

GnomAD4 genome AF: 0.000788 AC: 120 AN: 152302 Hom.: 5 Cov.: 33 AF XY: 0.000994 AC XY: 74 AN XY: 74482

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000653

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0226

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000273 Hom.: 0

Bravo AF: 0.000548

Asia WGS AF: 0.00953 AC: 33 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 21, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	3.8
Dann	Benign	0.65

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

Other links and lift over

dbSNP: rs2277634; hg19: chr17-48265209;