Variant rs28763878 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_000090.4(COL3A1):c.2661+22T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0337 in 1,613,042 control chromosomes in the GnomAD database, including 1,109 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.023 ( 44 hom., cov: 32)

Exomes 𝑓: 0.035 ( 1065 hom. )

Consequence

COL3A1
NM_000090.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.06

Variant links:

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 links:

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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=-0.6).

BP6

Variant 2-189003809-T-A is Benign according to our data. Variant chr2-189003809-T-A is described in ClinVar as [Benign]. Clinvar id is 254965.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-189003809-T-A is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0227 (3462/152304) while in subpopulation NFE AF= 0.0371 (2522/68022). AF 95% confidence interval is 0.0359. There are 44 homozygotes in gnomad4. There are 1592 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 44 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL3A1	NM_000090.4 linkuse as main transcript	c.2661+22T>A		intron_variant		ENST00000304636.9	NP_000081.2

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL3A1	ENST00000304636.9 linkuse as main transcript	c.2661+22T>A	intron_variant		1	NM_000090.4	ENSP00000304408	P1	P02461-1
COL3A1	ENST00000450867.2 linkuse as main transcript	c.2562+22T>A	intron_variant		1		ENSP00000415346
COL3A1	ENST00000467886.1 linkuse as main transcript	n.118T>A	non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes

AF:

0.0227

AC:

3462

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00734

Gnomad AMI

AF:

0.0154

Gnomad AMR

AF:

0.0194

Gnomad ASJ

AF:

0.0101

Gnomad EAS

AF:

0.000576

Gnomad SAS

AF:

0.0120

Gnomad FIN

AF:

0.0162

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0371

Gnomad OTH

AF:

0.0254

GnomAD3 exomes

AF:

0.0234

AC:

5888

AN:

251344

Hom.:

110

AF XY:

0.0233

AC XY:

3159

AN XY:

135834

show subpopulations

Gnomad AFR exome

AF:

0.00696

Gnomad AMR exome

AF:

0.0128

Gnomad ASJ exome

AF:

0.0141

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0114

Gnomad FIN exome

AF:

0.0182

Gnomad NFE exome

AF:

0.0379

Gnomad OTH exome

AF:

0.0220

GnomAD4 exome

AF:

0.0348

AC:

50883

AN:

1460738

Hom.:

1065

Cov.:

AF XY:

0.0339

AC XY:

24658

AN XY:

726796

show subpopulations

Gnomad4 AFR exome

AF:

0.00589

Gnomad4 AMR exome

AF:

0.0133

Gnomad4 ASJ exome

AF:

0.0137

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0118

Gnomad4 FIN exome

AF:

0.0174

Gnomad4 NFE exome

AF:

0.0414

Gnomad4 OTH exome

AF:

0.0295

GnomAD4 genome

AF:

0.0227

AC:

3462

AN:

152304

Hom.:

Cov.:

AF XY:

0.0214

AC XY:

1592

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.00731

Gnomad4 AMR

AF:

0.0193

Gnomad4 ASJ

AF:

0.0101

Gnomad4 EAS

AF:

0.000578

Gnomad4 SAS

AF:

0.0120

Gnomad4 FIN

AF:

0.0162

Gnomad4 NFE

AF:

0.0371

Gnomad4 OTH

AF:

0.0251

Alfa

AF:

0.0263

Hom.:

Bravo

AF:

0.0229

Asia WGS

AF:

0.00404

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

9.6

DANN

Benign

0.88

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