dbSNP rs200449080: COL3A1:c.3256-28G>A (chr2-189007472-G-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_000090.4(COL3A1):c.3256-28G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0072 in 1,550,406 control chromosomes in the GnomAD database, including 57 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.0057 ( 3 hom., cov: 31)

Exomes 𝑓: 0.0074 ( 54 hom. )

Consequence

COL3A1
NM_000090.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.235

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 -14 ACMG points.

BP4

This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 0 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 2-189007472-G-A is Benign according to our data. Variant chr2-189007472-G-A is described in ClinVar as [Benign]. Clinvar id is 254969.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-189007472-G-A is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00575 (874/152094) while in subpopulation NFE AF= 0.00921 (626/67994). AF 95% confidence interval is 0.00861. There are 3 homozygotes in gnomad4. There are 441 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL3A1	NM_000090.4 link	c.3256-28G>A		intron_variant	Intron 44 of 50	ENST00000304636.9	NP_000081.2	P02461-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL3A1	ENST00000304636.9 link	c.3256-28G>A		intron_variant	Intron 44 of 50	1	NM_000090.4	ENSP00000304408.4		P02461-1
COL3A1	ENST00000450867.2 link	c.3157-28G>A		intron_variant	Intron 43 of 49	1		ENSP00000415346.2		H7C435

Frequencies

GnomAD3 genomes

AF:

0.00575

AC:

874

AN:

151976

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00196

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00426

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.000387

Gnomad SAS

AF:

0.00208

Gnomad FIN

AF:

0.00794

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00921

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.00541

AC:

1216

AN:

224822

Hom.:

AF XY:

0.00537

AC XY:

651

AN XY:

121148

show subpopulations

Gnomad AFR exome

AF:

0.00107

Gnomad AMR exome

AF:

0.00225

Gnomad ASJ exome

AF:

0.000524

Gnomad EAS exome

AF:

0.00202

Gnomad SAS exome

AF:

0.00123

Gnomad FIN exome

AF:

0.00692

Gnomad NFE exome

AF:

0.00896

Gnomad OTH exome

AF:

0.00536

GnomAD4 exome

AF:

0.00736

AC:

10290

AN:

1398312

Hom.:

Cov.:

AF XY:

0.00715

AC XY:

4985

AN XY:

697042

show subpopulations

Gnomad4 AFR exome

AF:

0.00135

Gnomad4 AMR exome

AF:

0.00231

Gnomad4 ASJ exome

AF:

0.000785

Gnomad4 EAS exome

AF:

0.00107

Gnomad4 SAS exome

AF:

0.00125

Gnomad4 FIN exome

AF:

0.00823

Gnomad4 NFE exome

AF:

0.00872

Gnomad4 OTH exome

AF:

0.00514

GnomAD4 genome

AF:

0.00575

AC:

874

AN:

152094

Hom.:

Cov.:

AF XY:

0.00593

AC XY:

441

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.00195

Gnomad4 AMR

AF:

0.00426

Gnomad4 ASJ

AF:

0.000864

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.00208

Gnomad4 FIN

AF:

0.00794

Gnomad4 NFE

AF:

0.00921

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00884

Hom.:

Bravo

AF:

0.00471

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: 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

-0.81

CADD

Benign

DANN

Benign

0.73

BranchPoint Hunter

0.0

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