chr13-97300792-C-A

Variant names:

• chr13-97300792-C-A
• rs4441122
• NM_001382683.1:c.174+24383C>A

Variant summary

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

The NM_001382683.1(MBNL2):​c.174+24383C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.698 in 152,156 control chromosomes in the GnomAD database, including 37,214 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 0.70 (37214 hom., cov: 33)
• Consequence: MBNL2 NM_001382683.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.53
• Publications: 2 publications found

Genes affected

MBNL2 (HGNC:16746): (muscleblind like splicing regulator 2) This gene is a member of the muscleblind protein family which was initially described in Drosophila melanogaster. This gene encodes 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. Several alternatively spliced transcript variants have been described but the full-length natures of only some have been determined. [provided by RefSeq, Mar 2012]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.763 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MBNL2	NM_001382683.1	c.174+24383C>A		intron_variant	Intron 2 of 8	ENST00000679496.1	NP_001369612.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MBNL2	ENST00000679496.1	c.174+24383C>A		intron_variant	Intron 2 of 8		NM_001382683.1	ENSP00000505596.1

Frequencies

GnomAD3 genomes AF: 0.698 AC: 106082 AN: 152040 Hom.: 37176 Cov.: 33

Gnomad AFR AF: 0.770

Gnomad AMI AF: 0.610

Gnomad AMR AF: 0.651

Gnomad ASJ AF: 0.651

Gnomad EAS AF: 0.714

Gnomad SAS AF: 0.663

Gnomad FIN AF: 0.753

Gnomad MID AF: 0.680

Gnomad NFE AF: 0.661

Gnomad OTH AF: 0.689

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

GnomAD4 genome AF: 0.698 AC: 106165 AN: 152156 Hom.: 37214 Cov.: 33 AF XY: 0.702 AC XY: 52199 AN XY: 74392

African (AFR) AF: 0.770 AC: 31969 AN: 41508

American (AMR) AF: 0.651 AC: 9946 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.651 AC: 2255 AN: 3466

East Asian (EAS) AF: 0.713 AC: 3697 AN: 5186

South Asian (SAS) AF: 0.664 AC: 3200 AN: 4818

European-Finnish (FIN) AF: 0.753 AC: 7972 AN: 10586

Middle Eastern (MID) AF: 0.694 AC: 204 AN: 294

European-Non Finnish (NFE) AF: 0.661 AC: 44930 AN: 67998

Other (OTH) AF: 0.682 AC: 1437 AN: 2108

Alfa AF: 0.686 Hom.: 6276

Bravo AF: 0.689

Asia WGS AF: 0.657 AC: 2285 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.76
DANN	Benign	0.49
PhyloP100		-1.5
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: rs4441122; hg19: chr13-97953046;