2-188995684-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_000090.4(COL3A1):​c.1510-8C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000717 in 1,394,970 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

COL3A1
NM_000090.4 splice_region, intron

Scores

2
Splicing: ADA: 0.00004562
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.719
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]
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
COL3A1NM_000090.4 linkc.1510-8C>T splice_region_variant, intron_variant Intron 21 of 50 ENST00000304636.9 NP_000081.2 P02461-1
MIR3606NR_037401.1 linkn.55C>T non_coding_transcript_exon_variant Exon 1 of 1
MIR3606unassigned_transcript_524 n.14C>T non_coding_transcript_exon_variant Exon 1 of 1
MIR3606unassigned_transcript_523 n.*19C>T downstream_gene_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
COL3A1ENST00000304636.9 linkc.1510-8C>T splice_region_variant, intron_variant Intron 21 of 50 1 NM_000090.4 ENSP00000304408.4 P02461-1
COL3A1ENST00000450867.2 linkc.1411-8C>T splice_region_variant, intron_variant Intron 20 of 49 1 ENSP00000415346.2 H7C435
MIR3606ENST00000637672.1 linkn.55C>T non_coding_transcript_exon_variant Exon 1 of 1 6

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
7.17e-7
AC:
1
AN:
1394970
Hom.:
0
Cov.:
29
AF XY:
0.00
AC XY:
0
AN XY:
688400
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.30e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.81
CADD
Benign
6.0
DANN
Benign
0.25

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.000046
dbscSNV1_RF
Benign
0.0
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-189860410; API