2-170380611-C-G

Variant names:

• chr2-170380611-C-G
• rs10497367
• NM_138995.5:c.972-1405C>G

Variant summary

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

The ENST00000408978.9(MYO3B):​c.972-1405C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 152,146 control chromosomes in the GnomAD database, including 1,337 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 0.10 (1337 hom., cov: 33)
• Consequence: MYO3B ENST00000408978.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.522
• Publications: 0 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.476 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000408978.9. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO3B	NM_138995.5	MANE Select	c.972-1405C>G		intron	N/A	NP_620482.3
	MYO3B	NM_001083615.4		c.972-1405C>G		intron	N/A	NP_001077084.2
	MYO3B	NR_045682.2		n.1113-1405C>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO3B	ENST00000408978.9	TSL:1 MANE Select	c.972-1405C>G		intron	N/A	ENSP00000386213.4
	MYO3B	ENST00000409044.7	TSL:1	c.972-1405C>G		intron	N/A	ENSP00000386497.3
	MYO3B	ENST00000442690.1	TSL:1	c.969-1405C>G		intron	N/A	ENSP00000401160.1

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15478 AN: 152030 Hom.: 1334 Cov.: 33

Gnomad AFR AF: 0.0552

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.0398

Gnomad EAS AF: 0.493

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0884

Gnomad OTH AF: 0.0976

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

GnomAD4 genome AF: 0.102 AC: 15491 AN: 152146 Hom.: 1337 Cov.: 33 AF XY: 0.106 AC XY: 7866 AN XY: 74376

African (AFR) AF: 0.0551 AC: 2288 AN: 41512

American (AMR) AF: 0.153 AC: 2335 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0398 AC: 138 AN: 3470

East Asian (EAS) AF: 0.492 AC: 2536 AN: 5154

South Asian (SAS) AF: 0.142 AC: 685 AN: 4816

European-Finnish (FIN) AF: 0.109 AC: 1151 AN: 10594

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0884 AC: 6013 AN: 68012

Other (OTH) AF: 0.103 AC: 218 AN: 2110

Alfa AF: 0.0402 Hom.: 24

Bravo AF: 0.105

Asia WGS AF: 0.291 AC: 1011 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.9
DANN	Benign	0.70
PhyloP100		-0.52
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: rs10497367; hg19: chr2-171237121;