chr13-97302171-G-T

Variant names:

• chr13-97302171-G-T
• rs4771992
• NM_001382683.1:c.174+25762G>T

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+25762G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.689 in 152,012 control chromosomes in the GnomAD database, including 36,121 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 0.69 (36121 hom., cov: 31)
• Consequence: MBNL2 NM_001382683.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.223
• Publications: 6 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.719 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MBNL2	NM_001382683.1	c.174+25762G>T		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+25762G>T		intron_variant	Intron 2 of 8		NM_001382683.1	ENSP00000505596.1

Frequencies

GnomAD3 genomes AF: 0.689 AC: 104606 AN: 151894 Hom.: 36092 Cov.: 31

Gnomad AFR AF: 0.726

Gnomad AMI AF: 0.610

Gnomad AMR AF: 0.650

Gnomad ASJ AF: 0.651

Gnomad EAS AF: 0.717

Gnomad SAS AF: 0.663

Gnomad FIN AF: 0.762

Gnomad MID AF: 0.675

Gnomad NFE AF: 0.666

Gnomad OTH AF: 0.687

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

GnomAD4 genome AF: 0.689 AC: 104678 AN: 152012 Hom.: 36121 Cov.: 31 AF XY: 0.692 AC XY: 51452 AN XY: 74310

African (AFR) AF: 0.726 AC: 30072 AN: 41420

American (AMR) AF: 0.650 AC: 9925 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.651 AC: 2258 AN: 3466

East Asian (EAS) AF: 0.716 AC: 3688 AN: 5154

South Asian (SAS) AF: 0.663 AC: 3193 AN: 4814

European-Finnish (FIN) AF: 0.762 AC: 8060 AN: 10584

Middle Eastern (MID) AF: 0.688 AC: 201 AN: 292

European-Non Finnish (NFE) AF: 0.666 AC: 45292 AN: 67982

Other (OTH) AF: 0.680 AC: 1434 AN: 2110

Alfa AF: 0.671 Hom.: 61716

Bravo AF: 0.679

Asia WGS AF: 0.656 AC: 2280 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.3
DANN	Benign	0.67
PhyloP100		-0.22
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: rs4771992; hg19: chr13-97954425;