rs17283597

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001376819.1(MBNL1):​c.-790+16330A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0856 in 152,218 control chromosomes in the GnomAD database, including 690 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.086 ( 690 hom., cov: 32)

Consequence

MBNL1
NM_001376819.1 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.707
Variant links:
Genes affected
MBNL1 (HGNC:6923): (muscleblind like splicing regulator 1) This gene encodes a member of the muscleblind protein family which was initially described in Drosophila melanogaster. The encoded protein is a C3H-type zinc finger protein that modulates alternative splicing of pre-mRNAs. Muscleblind proteins bind specifically to expanded dsCUG RNA but not to normal size CUG repeats and may thereby play a role in the pathophysiology of myotonic dystrophy. Mice lacking this gene exhibited muscle abnormalities and cataracts. Several alternatively spliced transcript variants have been described but the full-length natures of only some have been determined. The different isoforms are thought to have different binding specificities and/or splicing activities. [provided by RefSeq, Sep 2015]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.118 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MBNL1NM_001376819.1 linkuse as main transcriptc.-790+16330A>G intron_variant NP_001363748.1
MBNL1NM_001387781.1 linkuse as main transcriptc.-790+16330A>G intron_variant NP_001374710.1
MBNL1NM_001387785.1 linkuse as main transcriptc.-790+16330A>G intron_variant NP_001374714.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MBNL1ENST00000477171.1 linkuse as main transcriptn.333+16330A>G intron_variant 3
MBNL1-AS1ENST00000669594.1 linkuse as main transcriptn.291+6638T>C intron_variant

Frequencies

GnomAD3 genomes
AF:
0.0856
AC:
13014
AN:
152100
Hom.:
688
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0346
Gnomad AMI
AF:
0.115
Gnomad AMR
AF:
0.0777
Gnomad ASJ
AF:
0.104
Gnomad EAS
AF:
0.0111
Gnomad SAS
AF:
0.0702
Gnomad FIN
AF:
0.107
Gnomad MID
AF:
0.142
Gnomad NFE
AF:
0.120
Gnomad OTH
AF:
0.0986
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.0856
AC:
13026
AN:
152218
Hom.:
690
Cov.:
32
AF XY:
0.0851
AC XY:
6335
AN XY:
74440
show subpopulations
Gnomad4 AFR
AF:
0.0347
Gnomad4 AMR
AF:
0.0776
Gnomad4 ASJ
AF:
0.104
Gnomad4 EAS
AF:
0.0112
Gnomad4 SAS
AF:
0.0704
Gnomad4 FIN
AF:
0.107
Gnomad4 NFE
AF:
0.120
Gnomad4 OTH
AF:
0.102
Alfa
AF:
0.106
Hom.:
409
Bravo
AF:
0.0807
Asia WGS
AF:
0.0530
AC:
185
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.83
CADD
Benign
0.20
DANN
Benign
0.68

Splicing

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.

Other links and lift over

dbSNP: rs17283597; hg19: chr3-151978559; API