Variant rs41265549 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.4011+34A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0288 in 1,606,222 control chromosomes in the GnomAD database, including 822 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.024 ( 84 hom., cov: 33)

Exomes 𝑓: 0.029 ( 738 hom. )

Consequence

COL3A1
NM_000090.4 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.657

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 2-189010399-A-G is Benign according to our data. Variant chr2-189010399-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 254971.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-189010399-A-G is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0236 (3597/152230) while in subpopulation NFE AF= 0.0303 (2062/68014). AF 95% confidence interval is 0.0292. There are 84 homozygotes in gnomad4. There are 1865 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 84 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL3A1	NM_000090.4 linkuse as main transcript	c.4011+34A>G		intron_variant		ENST00000304636.9

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL3A1	ENST00000304636.9 linkuse as main transcript	c.4011+34A>G	intron_variant		1	NM_000090.4	P1	P02461-1
COL3A1	ENST00000450867.2 linkuse as main transcript	c.3912+34A>G	intron_variant		1
COL3A1	ENST00000487010.1 linkuse as main transcript	n.1142A>G	non_coding_transcript_exon_variant	2/3	2

Frequencies

GnomAD3 genomes

AF:

0.0237

AC:

3599

AN:

152112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00466

Gnomad AMI

AF:

0.0121

Gnomad AMR

AF:

0.0185

Gnomad ASJ

AF:

0.0637

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0294

Gnomad FIN

AF:

0.0601

Gnomad MID

AF:

0.0446

Gnomad NFE

AF:

0.0303

Gnomad OTH

AF:

0.0167

GnomAD3 exomes

AF:

0.0294

AC:

7361

AN:

250684

Hom.:

166

AF XY:

0.0311

AC XY:

4212

AN XY:

135540

show subpopulations

Gnomad AFR exome

AF:

0.00426

Gnomad AMR exome

AF:

0.0154

Gnomad ASJ exome

AF:

0.0603

Gnomad EAS exome

AF:

0.0000545

Gnomad SAS exome

AF:

0.0273

Gnomad FIN exome

AF:

0.0546

Gnomad NFE exome

AF:

0.0347

Gnomad OTH exome

AF:

0.0332

GnomAD4 exome

AF:

0.0293

AC:

42662

AN:

1453992

Hom.:

738

Cov.:

AF XY:

0.0298

AC XY:

21552

AN XY:

723908

show subpopulations

Gnomad4 AFR exome

AF:

0.00469

Gnomad4 AMR exome

AF:

0.0154

Gnomad4 ASJ exome

AF:

0.0605

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0280

Gnomad4 FIN exome

AF:

0.0550

Gnomad4 NFE exome

AF:

0.0298

Gnomad4 OTH exome

AF:

0.0291

GnomAD4 genome

AF:

0.0236

AC:

3597

AN:

152230

Hom.:

Cov.:

AF XY:

0.0251

AC XY:

1865

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.00465

Gnomad4 AMR

AF:

0.0185

Gnomad4 ASJ

AF:

0.0637

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0292

Gnomad4 FIN

AF:

0.0601

Gnomad4 NFE

AF:

0.0303

Gnomad4 OTH

AF:

0.0166

Alfa

AF:

0.0319

Hom.:

Bravo

AF:

0.0201

Asia WGS

AF:

0.0130

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2018

This 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

-0.78

CADD

Benign

4.0

DANN

Benign

0.84

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