rs3765161

Variant names:

• chr2-189003684-C-T
• rs3765161
• NM_000090.4:c.2608-50C>T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000090.4(COL3A1):​c.2608-50C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0473 in 1,573,600 control chromosomes in the GnomAD database, including 5,249 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 0.12 (2459 hom., cov: 32)
  • Exomes 𝑓: 0.040 (2790 hom.)
• Consequence: COL3A1 NM_000090.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.57

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]

ACMG classification

Verdict is Benign. Variant got -20 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=-0.92).
• BP6: Variant 2-189003684-C-T is Benign according to our data. Variant chr2-189003684-C-T is described in ClinVar as [Benign]. Clinvar id is 254964.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.33 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL3A1	NM_000090.4	c.2608-50C>T		intron_variant	Intron 37 of 50	ENST00000304636.9	NP_000081.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL3A1	ENST00000304636.9	c.2608-50C>T		intron_variant	Intron 37 of 50	1	NM_000090.4	ENSP00000304408.4
COL3A1	ENST00000450867.2	c.2509-50C>T		intron_variant	Intron 36 of 49	1		ENSP00000415346.2
COL3A1	ENST00000467886.1	n.43-50C>T		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18115 AN: 151954 Hom.: 2438 Cov.: 32

Gnomad AFR AF: 0.334

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.0569

Gnomad ASJ AF: 0.0311

Gnomad EAS AF: 0.0908

Gnomad SAS AF: 0.0457

Gnomad FIN AF: 0.0214

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0321

Gnomad OTH AF: 0.101

GnomAD3 exomes AF: 0.0587 AC: 14734 AN: 250928 Hom.: 1147 AF XY: 0.0534 AC XY: 7247 AN XY: 135664

Gnomad AFR exome AF: 0.342

Gnomad AMR exome AF: 0.0346

Gnomad ASJ exome AF: 0.0247

Gnomad EAS exome AF: 0.0950

Gnomad SAS exome AF: 0.0457

Gnomad FIN exome AF: 0.0244

Gnomad NFE exome AF: 0.0334

Gnomad OTH exome AF: 0.0510

GnomAD4 exome AF: 0.0395 AC: 56201 AN: 1421528 Hom.: 2790 Cov.: 27 AF XY: 0.0387 AC XY: 27498 AN XY: 709814

Gnomad4 AFR exome AF: 0.341

Gnomad4 AMR exome AF: 0.0370

Gnomad4 ASJ exome AF: 0.0241

Gnomad4 EAS exome AF: 0.0838

Gnomad4 SAS exome AF: 0.0435

Gnomad4 FIN exome AF: 0.0248

Gnomad4 NFE exome AF: 0.0287

Gnomad4 OTH exome AF: 0.0552

GnomAD4 genome AF: 0.120 AC: 18185 AN: 152072 Hom.: 2459 Cov.: 32 AF XY: 0.117 AC XY: 8696 AN XY: 74338

Gnomad4 AFR AF: 0.335

Gnomad4 AMR AF: 0.0567

Gnomad4 ASJ AF: 0.0311

Gnomad4 EAS AF: 0.0906

Gnomad4 SAS AF: 0.0459

Gnomad4 FIN AF: 0.0214

Gnomad4 NFE AF: 0.0321

Gnomad4 OTH AF: 0.100

Alfa AF: 0.0781 Hom.: 275

Bravo AF: 0.131

Asia WGS AF: 0.0920 AC: 319 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 18, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

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	-0.92
CADD	Benign	0.068
DANN	Benign	0.43
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

Other links and lift over

dbSNP: rs3765161; hg19: chr2-189868410;