rs323622

Positions:

• chr3-152256165-T-A
• chr3-152256165-T-C

Variant summary

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

The NM_001376819.1(MBNL1):​c.-790+11725T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.462 in 152,040 control chromosomes in the GnomAD database, including 17,511 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 0.46 (17511 hom., cov: 32)
• Consequence: MBNL1 NM_001376819.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.10

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]

MBNL1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.565 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MBNL1	NM_001376819.1	c.-790+11725T>A		intron_variant			NP_001363748.1
MBNL1	NM_001387781.1	c.-790+11725T>A		intron_variant			NP_001374710.1
MBNL1	NM_001387785.1	c.-790+11725T>A		intron_variant			NP_001374714.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MBNL1	ENST00000477171.1	n.333+11725T>A		intron_variant		3
MBNL1-AS1	ENST00000669594.1	n.292-9261A>T		intron_variant

Frequencies

GnomAD3 genomes AF: 0.462 AC: 70183 AN: 151922 Hom.: 17515 Cov.: 32

Gnomad AFR AF: 0.258

Gnomad AMI AF: 0.567

Gnomad AMR AF: 0.529

Gnomad ASJ AF: 0.605

Gnomad EAS AF: 0.468

Gnomad SAS AF: 0.583

Gnomad FIN AF: 0.550

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.539

Gnomad OTH AF: 0.482

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

GnomAD4 genome AF: 0.462 AC: 70187 AN: 152040 Hom.: 17511 Cov.: 32 AF XY: 0.465 AC XY: 34544 AN XY: 74314

Gnomad4 AFR AF: 0.257

Gnomad4 AMR AF: 0.529

Gnomad4 ASJ AF: 0.605

Gnomad4 EAS AF: 0.467

Gnomad4 SAS AF: 0.583

Gnomad4 FIN AF: 0.550

Gnomad4 NFE AF: 0.539

Gnomad4 OTH AF: 0.477

Alfa AF: 0.479 Hom.: 2223

Bravo AF: 0.450

Asia WGS AF: 0.461 AC: 1606 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.6
DANN	Benign	0.70

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs323622; hg19: chr3-151973954;