3-152282140-A-G

Variant names:

• chr3-152282140-A-G
• rs755763
• NM_021038.5:c.-790+13048A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021038.5(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 NM_021038.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.568
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021038.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MBNL1	NM_021038.5	MANE Select	c.-790+13048A>G		intron	N/A	NP_066368.2
	MBNL1	NM_001376818.1		c.-790+13048A>G		intron	N/A	NP_001363747.1
	MBNL1	NM_001376819.1		c.-789-17265A>G		intron	N/A	NP_001363748.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MBNL1	ENST00000324210.10	TSL:1 MANE Select	c.-790+13048A>G		intron	N/A	ENSP00000319429.5	Q9NR56-5
	MBNL1	ENST00000355460.6	TSL:1	c.-790+13048A>G		intron	N/A	ENSP00000347637.2	Q9NR56-2
	MBNL1	ENST00000493459.5	TSL:1	c.-176+13048A>G		intron	N/A	ENSP00000419347.1	Q86VM6

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

African (AFR) AF: 0.945 AC: 39256 AN: 41538

American (AMR) AF: 0.742 AC: 11332 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.726 AC: 2522 AN: 3472

East Asian (EAS) AF: 0.815 AC: 4222 AN: 5178

South Asian (SAS) AF: 0.684 AC: 3295 AN: 4820

European-Finnish (FIN) AF: 0.607 AC: 6395 AN: 10542

Middle Eastern (MID) AF: 0.793 AC: 233 AN: 294

European-Non Finnish (NFE) AF: 0.733 AC: 49841 AN: 67956

Other (OTH) AF: 0.793 AC: 1669 AN: 2104

Alfa AF: 0.744 Hom.: 23363

Bravo AF: 0.806

Asia WGS AF: 0.768 AC: 2669 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.1
DANN	Benign	0.52
PhyloP100		-0.57
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs755763; hg19: chr3-151999929;