rs9556711

Variant names:

• chr13-97364162-G-A
• rs9556711
• NM_001382683.1:c.1013-974G>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.1013-974G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 152,048 control chromosomes in the GnomAD database, including 5,949 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 0.20 (5949 hom., cov: 32)
• Consequence: MBNL2 NM_001382683.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.587
• Publications: 12 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.507 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MBNL2	NM_001382683.1	c.1013-974G>A		intron_variant	Intron 7 of 8	ENST00000679496.1	NP_001369612.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MBNL2	ENST00000679496.1	c.1013-974G>A		intron_variant	Intron 7 of 8		NM_001382683.1	ENSP00000505596.1

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30012 AN: 151930 Hom.: 5928 Cov.: 32

Gnomad AFR AF: 0.512

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.0412

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0660

Gnomad OTH AF: 0.151

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

GnomAD4 genome AF: 0.198 AC: 30075 AN: 152048 Hom.: 5949 Cov.: 32 AF XY: 0.194 AC XY: 14436 AN XY: 74320

African (AFR) AF: 0.513 AC: 21234 AN: 41420

American (AMR) AF: 0.103 AC: 1571 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 379 AN: 3470

East Asian (EAS) AF: 0.192 AC: 993 AN: 5168

South Asian (SAS) AF: 0.121 AC: 583 AN: 4824

European-Finnish (FIN) AF: 0.0412 AC: 436 AN: 10576

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.0660 AC: 4490 AN: 67992

Other (OTH) AF: 0.151 AC: 319 AN: 2108

Alfa AF: 0.104 Hom.: 8391

Bravo AF: 0.217

Asia WGS AF: 0.190 AC: 662 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.24
DANN	Benign	0.54
PhyloP100		-0.59
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: rs9556711; hg19: chr13-98016416;