2-170244999-A-G

Position:

• chr2-170244999-A-G

Variant summary

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

The NM_138995.5(MYO3B):​c.749+8863A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.491 in 152,008 control chromosomes in the GnomAD database, including 19,180 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 0.49 (19180 hom., cov: 32)
• Consequence: MYO3B NM_138995.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.233

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.696 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO3B	NM_138995.5	c.749+8863A>G		intron_variant		ENST00000408978.9	NP_620482.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYO3B	ENST00000408978.9	c.749+8863A>G		intron_variant		1	NM_138995.5	ENSP00000386213	P1

Frequencies

GnomAD3 genomes AF: 0.491 AC: 74626 AN: 151890 Hom.: 19188 Cov.: 32

Gnomad AFR AF: 0.347

Gnomad AMI AF: 0.657

Gnomad AMR AF: 0.617

Gnomad ASJ AF: 0.499

Gnomad EAS AF: 0.716

Gnomad SAS AF: 0.600

Gnomad FIN AF: 0.536

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.517

Gnomad OTH AF: 0.476

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

GnomAD4 genome AF: 0.491 AC: 74627 AN: 152008 Hom.: 19180 Cov.: 32 AF XY: 0.498 AC XY: 37059 AN XY: 74344

Gnomad4 AFR AF: 0.346

Gnomad4 AMR AF: 0.617

Gnomad4 ASJ AF: 0.499

Gnomad4 EAS AF: 0.715

Gnomad4 SAS AF: 0.599

Gnomad4 FIN AF: 0.536

Gnomad4 NFE AF: 0.517

Gnomad4 OTH AF: 0.479

Alfa AF: 0.518 Hom.: 42597

Bravo AF: 0.488

Asia WGS AF: 0.633 AC: 2202 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.4
DANN	Benign	0.38

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: rs2355351; hg19: chr2-171101509;