rs7561268

Positions:

• chr2-170400087-A-C

Variant summary

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

The NM_138995.5(MYO3B):​c.1792-101A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.543 in 1,477,614 control chromosomes in the GnomAD database, including 222,123 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 (18949 hom., cov: 31)
  • Exomes 𝑓: 0.55 (203174 hom.)
• Consequence: MYO3B NM_138995.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0730

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]

MYO3B-AS1 (HGNC:40713): (MYO3B antisense RNA 1)

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 (EAS) allele frequency at 95% confidence interval = 0.615 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO3B	NM_138995.5	c.1792-101A>C		intron_variant		ENST00000408978.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO3B	ENST00000408978.9	c.1792-101A>C		intron_variant		1	NM_138995.5	P1
MYO3B-AS1	ENST00000625968.2	n.53+8425T>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.493 AC: 74825 AN: 151846 Hom.: 18926 Cov.: 31

Gnomad AFR AF: 0.390

Gnomad AMI AF: 0.592

Gnomad AMR AF: 0.377

Gnomad ASJ AF: 0.503

Gnomad EAS AF: 0.633

Gnomad SAS AF: 0.552

Gnomad FIN AF: 0.539

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.558

Gnomad OTH AF: 0.483

GnomAD4 exome AF: 0.549 AC: 727965 AN: 1325650 Hom.: 203174 AF XY: 0.550 AC XY: 361219 AN XY: 656946

Gnomad4 AFR exome AF: 0.387

Gnomad4 AMR exome AF: 0.299

Gnomad4 ASJ exome AF: 0.495

Gnomad4 EAS exome AF: 0.632

Gnomad4 SAS exome AF: 0.555

Gnomad4 FIN exome AF: 0.550

Gnomad4 NFE exome AF: 0.563

Gnomad4 OTH exome AF: 0.536

GnomAD4 genome AF: 0.493 AC: 74888 AN: 151964 Hom.: 18949 Cov.: 31 AF XY: 0.491 AC XY: 36465 AN XY: 74266

Gnomad4 AFR AF: 0.390

Gnomad4 AMR AF: 0.376

Gnomad4 ASJ AF: 0.503

Gnomad4 EAS AF: 0.633

Gnomad4 SAS AF: 0.551

Gnomad4 FIN AF: 0.539

Gnomad4 NFE AF: 0.558

Gnomad4 OTH AF: 0.487

Alfa AF: 0.540 Hom.: 45676

Bravo AF: 0.472

Asia WGS AF: 0.602 AC: 2095 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	1.4
DANN	Benign	0.75

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: rs7561268; hg19: chr2-171256597; COSMIC: COSV58704238;