rs4793874

Variant names:

• chr17-57577205-C-A
• rs4793874
• NM_138962.4:c.455-19663C>A

Variant summary

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

The NM_138962.4(MSI2):​c.455-19663C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0718 in 152,256 control chromosomes in the GnomAD database, including 495 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 0.072 (495 hom., cov: 32)
• Consequence: MSI2 NM_138962.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0840
• Publications: 2 publications found

Genes affected

MSI2 (HGNC:18585): (musashi RNA binding protein 2) This gene encodes an RNA-binding protein that is a member of the Musashi protein family. The encoded protein is transcriptional regulator that targets genes involved in development and cell cycle regulation. Mutations in this gene are associated with poor prognosis in certain types of cancers. This gene has also been shown to be rearranged in certain cancer cells. [provided by RefSeq, Apr 2016]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MSI2	NM_138962.4	c.455-19663C>A		intron_variant	Intron 7 of 13	ENST00000284073.7	NP_620412.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MSI2	ENST00000284073.7	c.455-19663C>A		intron_variant	Intron 7 of 13	1	NM_138962.4	ENSP00000284073.2

Frequencies

GnomAD3 genomes AF: 0.0718 AC: 10925 AN: 152138 Hom.: 495 Cov.: 32

Gnomad AFR AF: 0.0212

Gnomad AMI AF: 0.0461

Gnomad AMR AF: 0.0633

Gnomad ASJ AF: 0.120

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0643

Gnomad FIN AF: 0.0615

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.0900

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

GnomAD4 genome AF: 0.0718 AC: 10926 AN: 152256 Hom.: 495 Cov.: 32 AF XY: 0.0690 AC XY: 5140 AN XY: 74448

African (AFR) AF: 0.0212 AC: 880 AN: 41548

American (AMR) AF: 0.0633 AC: 968 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 417 AN: 3468

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5186

South Asian (SAS) AF: 0.0639 AC: 308 AN: 4820

European-Finnish (FIN) AF: 0.0615 AC: 652 AN: 10604

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.109 AC: 7428 AN: 68016

Other (OTH) AF: 0.0891 AC: 188 AN: 2110

Alfa AF: 0.0962 Hom.: 392

Bravo AF: 0.0699

Asia WGS AF: 0.0220 AC: 76 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	9.0
DANN	Benign	0.81
PhyloP100		-0.084
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: rs4793874; hg19: chr17-55654566;