2-188985152-G-T

Variant names:

• chr2-188985152-G-T
• rs150919697
• NM_000090.4:c.283-45G>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_000090.4(COL3A1):​c.283-45G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0041 in 1,576,442 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0026 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0043 (17 hom.)
• Consequence: COL3A1 NM_000090.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.18
• Publications: 0 publications found

Genes affected

COL3A1 (HGNC:2201): (collagen type III alpha 1 chain) This gene encodes the pro-alpha1 chains of type III collagen, a fibrillar collagen that is found in extensible connective tissues such as skin, lung, uterus, intestine and the vascular system, frequently in association with type I collagen. Mutations in this gene are associated with Ehlers-Danlos syndrome type IV, and with aortic and arterial aneurysms. [provided by R. Dalgleish, Feb 2008]

COL3A1 Gene-Disease associations (from GenCC):

• autosomal dominant Ehlers-Danlos syndrome, vascular type

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, Genomics England PanelApp
• Ehlers-Danlos syndrome, vascular type

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
• polymicrogyria with or without vascular-type Ehlers-Danlos syndrome

  Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 2-188985152-G-T is Benign according to our data. Variant chr2-188985152-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 254966.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00257 (391/151990) while in subpopulation NFE AF = 0.00436 (296/67908). AF 95% confidence interval is 0.00395. There are 2 homozygotes in GnomAd4. There are 171 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL3A1	NM_000090.4	c.283-45G>T		intron_variant	Intron 2 of 50	ENST00000304636.9	NP_000081.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL3A1	ENST00000304636.9	c.283-45G>T		intron_variant	Intron 2 of 50	1	NM_000090.4	ENSP00000304408.4

Frequencies

GnomAD3 genomes AF: 0.00258 AC: 392 AN: 151872 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00106

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00112

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00245

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00437

Gnomad OTH AF: 0.000959

GnomAD2 exomes AF: 0.00259 AC: 648 AN: 250254 AF XY: 0.00248

Gnomad AFR exome AF: 0.000740

Gnomad AMR exome AF: 0.000874

Gnomad ASJ exome AF: 0.000597

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00362

Gnomad NFE exome AF: 0.00452

Gnomad OTH exome AF: 0.00181

GnomAD4 exome AF: 0.00426 AC: 6072 AN: 1424452 Hom.: 17 Cov.: 28 AF XY: 0.00406 AC XY: 2890 AN XY: 711202

African (AFR) AF: 0.000766 AC: 25 AN: 32650

American (AMR) AF: 0.000832 AC: 37 AN: 44486

Ashkenazi Jewish (ASJ) AF: 0.000464 AC: 12 AN: 25848

East Asian (EAS) AF: 0.00 AC: 0 AN: 39498

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85472

European-Finnish (FIN) AF: 0.00373 AC: 199 AN: 53332

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5702

European-Non Finnish (NFE) AF: 0.00523 AC: 5636 AN: 1078416

Other (OTH) AF: 0.00274 AC: 162 AN: 59048

GnomAD4 genome AF: 0.00257 AC: 391 AN: 151990 Hom.: 2 Cov.: 32 AF XY: 0.00230 AC XY: 171 AN XY: 74282

African (AFR) AF: 0.00106 AC: 44 AN: 41502

American (AMR) AF: 0.00112 AC: 17 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3464

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5154

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00245 AC: 26 AN: 10592

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00436 AC: 296 AN: 67908

Other (OTH) AF: 0.000949 AC: 2 AN: 2108

Alfa AF: 0.00122 Hom.: 0

Bravo AF: 0.00231

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.94
DANN	Benign	0.71
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs150919697; hg19: chr2-189849878;