rs2118674

Positions:

• chr2-170462384-A-T

Variant summary

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

The NM_138995.5(MYO3B):​c.2731-984A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.874 in 152,236 control chromosomes in the GnomAD database, including 59,492 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 0.87 (59492 hom., cov: 33)
• Consequence: MYO3B NM_138995.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.240

Genes affected

MYO3B (HGNC:15576): (myosin IIIB) This gene encodes one of the class III myosins. Myosins are ATPases, activated by actin, that move along actin filaments in the cell. This class of myosins are characterized by an amino-terminal kinase domain and shown to be present in photoreceptors. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.96 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO3B	NM_138995.5	c.2731-984A>T		intron_variant		ENST00000408978.9	NP_620482.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYO3B	ENST00000408978.9	c.2731-984A>T		intron_variant		1	NM_138995.5	ENSP00000386213	P1

Frequencies

GnomAD3 genomes AF: 0.874 AC: 132960 AN: 152118 Hom.: 59473 Cov.: 33

Gnomad AFR AF: 0.667

Gnomad AMI AF: 0.986

Gnomad AMR AF: 0.935

Gnomad ASJ AF: 0.919

Gnomad EAS AF: 0.763

Gnomad SAS AF: 0.964

Gnomad FIN AF: 0.988

Gnomad MID AF: 0.908

Gnomad NFE AF: 0.966

Gnomad OTH AF: 0.890

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

GnomAD4 genome AF: 0.874 AC: 133025 AN: 152236 Hom.: 59492 Cov.: 33 AF XY: 0.876 AC XY: 65248 AN XY: 74450

Gnomad4 AFR AF: 0.666

Gnomad4 AMR AF: 0.935

Gnomad4 ASJ AF: 0.919

Gnomad4 EAS AF: 0.763

Gnomad4 SAS AF: 0.964

Gnomad4 FIN AF: 0.988

Gnomad4 NFE AF: 0.966

Gnomad4 OTH AF: 0.886

Alfa AF: 0.916 Hom.: 8139

Bravo AF: 0.857

Asia WGS AF: 0.858 AC: 2985 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.081
DANN	Benign	0.62

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

Publications

LitVar

Other links and lift over

dbSNP: rs2118674; hg19: chr2-171318894;