rs10194304

Positions:

• chr2-189006901-C-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.3202-36C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0357 in 1,605,714 control chromosomes in the GnomAD database, including 2,690 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.086 (1189 hom., cov: 31)
  • Exomes 𝑓: 0.031 (1501 hom.)
• Consequence: COL3A1 NM_000090.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.23

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: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 2-189006901-C-T is Benign according to our data. Variant chr2-189006901-C-T is described in ClinVar as [Benign]. Clinvar id is 254967.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.233 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL3A1	NM_000090.4	c.3202-36C>T		intron_variant		ENST00000304636.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL3A1	ENST00000304636.9	c.3202-36C>T		intron_variant		1	NM_000090.4	P1
COL3A1	ENST00000450867.2	c.3103-36C>T		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.0854 AC: 12951 AN: 151590 Hom.: 1185 Cov.: 31

Gnomad AFR AF: 0.237

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0439

Gnomad ASJ AF: 0.0263

Gnomad EAS AF: 0.00700

Gnomad SAS AF: 0.0164

Gnomad FIN AF: 0.0185

Gnomad MID AF: 0.0414

Gnomad NFE AF: 0.0286

Gnomad OTH AF: 0.0677

GnomAD3 exomes AF: 0.0387 AC: 9722 AN: 251022 Hom.: 515 AF XY: 0.0346 AC XY: 4701 AN XY: 135700

Gnomad AFR exome AF: 0.242

Gnomad AMR exome AF: 0.0281

Gnomad ASJ exome AF: 0.0196

Gnomad EAS exome AF: 0.00756

Gnomad SAS exome AF: 0.0155

Gnomad FIN exome AF: 0.0207

Gnomad NFE exome AF: 0.0295

Gnomad OTH exome AF: 0.0379

GnomAD4 exome AF: 0.0305 AC: 44357 AN: 1454004 Hom.: 1501 Cov.: 30 AF XY: 0.0295 AC XY: 21346 AN XY: 723758

Gnomad4 AFR exome AF: 0.241

Gnomad4 AMR exome AF: 0.0296

Gnomad4 ASJ exome AF: 0.0200

Gnomad4 EAS exome AF: 0.00624

Gnomad4 SAS exome AF: 0.0145

Gnomad4 FIN exome AF: 0.0214

Gnomad4 NFE exome AF: 0.0265

Gnomad4 OTH exome AF: 0.0387

GnomAD4 genome AF: 0.0856 AC: 12983 AN: 151710 Hom.: 1189 Cov.: 31 AF XY: 0.0833 AC XY: 6172 AN XY: 74110

Gnomad4 AFR AF: 0.237

Gnomad4 AMR AF: 0.0438

Gnomad4 ASJ AF: 0.0263

Gnomad4 EAS AF: 0.00701

Gnomad4 SAS AF: 0.0162

Gnomad4 FIN AF: 0.0185

Gnomad4 NFE AF: 0.0286

Gnomad4 OTH AF: 0.0670

Alfa AF: 0.0480 Hom.: 122

Bravo AF: 0.0934

Asia WGS AF: 0.0230 AC: 83 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 18, 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	-0.81
CADD	Benign	7.3
DANN	Benign	0.62

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: rs10194304; hg19: chr2-189871627;