chr3-152282140-A-G

Position:

• chr3-152282140-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000324210.10(MBNL1):​c.-790+13048A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.785 in 152,084 control chromosomes in the GnomAD database, including 47,813 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 0.79 (47813 hom., cov: 32)
• Consequence: MBNL1 ENST00000324210.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.568

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.937 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MBNL1	NM_021038.5	c.-790+13048A>G		intron_variant		ENST00000324210.10	NP_066368.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MBNL1	ENST00000324210.10	c.-790+13048A>G		intron_variant		1	NM_021038.5	ENSP00000319429.5

Frequencies

GnomAD3 genomes AF: 0.785 AC: 119309 AN: 151966 Hom.: 47760 Cov.: 32

Gnomad AFR AF: 0.945

Gnomad AMI AF: 0.715

Gnomad AMR AF: 0.743

Gnomad ASJ AF: 0.726

Gnomad EAS AF: 0.816

Gnomad SAS AF: 0.685

Gnomad FIN AF: 0.607

Gnomad MID AF: 0.785

Gnomad NFE AF: 0.733

Gnomad OTH AF: 0.791

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

GnomAD4 genome AF: 0.785 AC: 119417 AN: 152084 Hom.: 47813 Cov.: 32 AF XY: 0.778 AC XY: 57786 AN XY: 74322

Gnomad4 AFR AF: 0.945

Gnomad4 AMR AF: 0.742

Gnomad4 ASJ AF: 0.726

Gnomad4 EAS AF: 0.815

Gnomad4 SAS AF: 0.684

Gnomad4 FIN AF: 0.607

Gnomad4 NFE AF: 0.733

Gnomad4 OTH AF: 0.793

Alfa AF: 0.744 Hom.: 21210

Bravo AF: 0.806

Asia WGS AF: 0.768 AC: 2669 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.1
DANN	Benign	0.52

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: rs755763; hg19: chr3-151999929;