rs7561268

Variant names:

• chr2-170400087-A-C
• rs7561268
• NM_138995.5:c.1792-101A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
MYO3B	NM_138995.5	c.1792-101A>C		intron_variant	Intron 16 of 34	ENST00000408978.9	NP_620482.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO3B	ENST00000408978.9	c.1792-101A>C		intron_variant	Intron 16 of 34	1	NM_138995.5	ENSP00000386213.4

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

African (AFR) AF: 0.387 AC: 11726 AN: 30284

American (AMR) AF: 0.299 AC: 11705 AN: 39198

Ashkenazi Jewish (ASJ) AF: 0.495 AC: 11378 AN: 22990

East Asian (EAS) AF: 0.632 AC: 24249 AN: 38370

South Asian (SAS) AF: 0.555 AC: 41396 AN: 74632

European-Finnish (FIN) AF: 0.550 AC: 27824 AN: 50634

Middle Eastern (MID) AF: 0.463 AC: 2298 AN: 4966

European-Non Finnish (NFE) AF: 0.563 AC: 567842 AN: 1009480

Other (OTH) AF: 0.536 AC: 29547 AN: 55096

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

African (AFR) AF: 0.390 AC: 16181 AN: 41446

American (AMR) AF: 0.376 AC: 5750 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.503 AC: 1745 AN: 3468

East Asian (EAS) AF: 0.633 AC: 3262 AN: 5152

South Asian (SAS) AF: 0.551 AC: 2659 AN: 4822

European-Finnish (FIN) AF: 0.539 AC: 5680 AN: 10534

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.558 AC: 37919 AN: 67946

Other (OTH) AF: 0.487 AC: 1030 AN: 2114

Alfa AF: 0.529 Hom.: 73077

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
PhyloP100		0.073
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: rs7561268; hg19: chr2-171256597; COSMIC: COSV58704238;