Variant 3-152268473-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000355460.6(MBNL1):c.-1409C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0619 in 310,936 control chromosomes in the GnomAD database, including 841 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.059 ( 385 hom., cov: 32)

Exomes 𝑓: 0.065 ( 456 hom. )

Consequence

MBNL1
ENST00000355460.6 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.41

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]

MBNL1 links:

MBNL1-AS1 (HGNC:44584): (MBNL1 antisense RNA 1)

MBNL1-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 3-152268473-C-T is Benign according to our data. Variant chr3-152268473-C-T is described in ClinVar as [Benign]. Clinvar id is 218788.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.084 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MBNL1-AS1	NR_027037.1 linkuse as main transcript	n.788G>A		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	Protein	Appris	UniProt
MBNL1	ENST00000355460.6 linkuse as main transcript	c.-1409C>T	5_prime_UTR_variant	1/9	1	ENSP00000347637	A1	Q9NR56-2
MBNL1	ENST00000282486.10 linkuse as main transcript	c.-1409C>T	5_prime_UTR_variant	1/10	5	ENSP00000282486	P4	Q9NR56-1
MBNL1	ENST00000282488.11 linkuse as main transcript	c.-1409C>T	5_prime_UTR_variant	1/11	5	ENSP00000282488	A1

Frequencies

GnomAD3 genomes

AF:

0.0587

AC:

8931

AN:

152194

Hom.:

385

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0151

Gnomad AMI

AF:

0.0549

Gnomad AMR

AF:

0.0496

Gnomad ASJ

AF:

0.0334

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0219

Gnomad FIN

AF:

0.124

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0858

Gnomad OTH

AF:

0.0559

GnomAD4 exome

AF:

0.0650

AC:

10310

AN:

158624

Hom.:

456

Cov.:

AF XY:

0.0586

AC XY:

5120

AN XY:

87374

show subpopulations

Gnomad4 AFR exome

AF:

0.00923

Gnomad4 AMR exome

AF:

0.0463

Gnomad4 ASJ exome

AF:

0.0302

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0258

Gnomad4 FIN exome

AF:

0.125

Gnomad4 NFE exome

AF:

0.0820

Gnomad4 OTH exome

AF:

0.0674

GnomAD4 genome

AF:

0.0587

AC:

8934

AN:

152312

Hom.:

385

Cov.:

AF XY:

0.0591

AC XY:

4400

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.0150

Gnomad4 AMR

AF:

0.0495

Gnomad4 ASJ

AF:

0.0334

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0221

Gnomad4 FIN

AF:

0.124

Gnomad4 NFE

AF:

0.0859

Gnomad4 OTH

AF:

0.0553

Alfa

AF:

0.0732

Hom.:

454

Bravo

AF:

0.0504

Asia WGS

AF:

0.0130

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia

Jul 10, 2015

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

0.68

DANN

Benign

0.86

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over