2-188995402-C-T

Variant names:

• chr2-188995402-C-T
• rs3106798
• NM_000090.4:c.1510-290C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000090.4(COL3A1):​c.1510-290C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 152,098 control chromosomes in the GnomAD database, including 11,614 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.36 (11614 hom., cov: 32)
• Consequence: COL3A1 NM_000090.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.806
• Publications: 2 publications found

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]

MIR3606 (HGNC:38881): (microRNA 3606) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 2-188995402-C-T is Benign according to our data. Variant chr2-188995402-C-T is described in ClinVar as [Benign]. Clinvar id is 670964.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.588 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL3A1	NM_000090.4	c.1510-290C>T		intron_variant	Intron 21 of 50	ENST00000304636.9	NP_000081.2
MIR3606	NR_037401.1	n.-228C>T		upstream_gene_variant
MIR3606	unassigned_transcript_523	n.-243C>T		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL3A1	ENST00000304636.9	c.1510-290C>T		intron_variant	Intron 21 of 50	1	NM_000090.4	ENSP00000304408.4

Frequencies

GnomAD3 genomes AF: 0.356 AC: 54144 AN: 151980 Hom.: 11612 Cov.: 32

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.435

Gnomad AMR AF: 0.448

Gnomad ASJ AF: 0.309

Gnomad EAS AF: 0.606

Gnomad SAS AF: 0.462

Gnomad FIN AF: 0.558

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.429

Gnomad OTH AF: 0.328

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.356 AC: 54153 AN: 152098 Hom.: 11614 Cov.: 32 AF XY: 0.365 AC XY: 27149 AN XY: 74346

African (AFR) AF: 0.112 AC: 4656 AN: 41516

American (AMR) AF: 0.448 AC: 6848 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.309 AC: 1071 AN: 3470

East Asian (EAS) AF: 0.605 AC: 3125 AN: 5162

South Asian (SAS) AF: 0.463 AC: 2233 AN: 4826

European-Finnish (FIN) AF: 0.558 AC: 5891 AN: 10552

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.429 AC: 29161 AN: 67968

Other (OTH) AF: 0.329 AC: 695 AN: 2114

Alfa AF: 0.402 Hom.: 4481

Bravo AF: 0.338

Asia WGS AF: 0.500 AC: 1739 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.28
DANN	Benign	0.67
PhyloP100		-0.81
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3106798; hg19: chr2-189860128;