rs3773908

chr3-152417319-G-Achr3-152417319-G-Cchr3-152417319-G-T

Variant summary

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

The NM_021038.5(MBNL1):c.345+2208G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.745 in 152,080 control chromosomes in the GnomAD database, including 42,839 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 0.75 (42839 hom., cov: 32)
• Consequence: MBNL1 NM_021038.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.129

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.866 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MBNL1	NM_021038.5	c.345+2208G>A		intron_variant		ENST00000324210.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MBNL1	ENST00000324210.10	c.345+2208G>A		intron_variant		1	NM_021038.5	A1

Frequencies

GnomAD3 genomes AF: 0.745 AC: 113192 AN: 151962 Hom.: 42780 Cov.: 32

Gnomad AFR AF: 0.873

Gnomad AMI AF: 0.699

Gnomad AMR AF: 0.718

Gnomad ASJ AF: 0.693

Gnomad EAS AF: 0.836

Gnomad SAS AF: 0.658

Gnomad FIN AF: 0.615

Gnomad MID AF: 0.756

Gnomad NFE AF: 0.696

Gnomad OTH AF: 0.741

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

GnomAD4 genome AF: 0.745 AC: 113307 AN: 152080 Hom.: 42839 Cov.: 32 AF XY: 0.741 AC XY: 55055 AN XY: 74312

Gnomad4 AFR AF: 0.874

Gnomad4 AMR AF: 0.717

Gnomad4 ASJ AF: 0.693

Gnomad4 EAS AF: 0.835

Gnomad4 SAS AF: 0.657

Gnomad4 FIN AF: 0.615

Gnomad4 NFE AF: 0.696

Gnomad4 OTH AF: 0.744

Alfa AF: 0.715 Hom.: 64929

Bravo AF: 0.759

Asia WGS AF: 0.761 AC: 2647 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	1.4
Dann	Benign	0.22

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: rs3773908; hg19: chr3-152135108;