2-191390304-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_001130158.3(MYO1B):c.1794G>A(p.Pro598=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00296 in 1,613,230 control chromosomes in the GnomAD database, including 117 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.016 (62 hom., cov: 33)
  • Exomes 𝑓: 0.0016 (55 hom.)
• Consequence: MYO1B NM_001130158.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.928

Genes affected

MYO1B (HGNC:7596): (myosin IB) Enables ATP binding activity; actin filament binding activity; and microfilament motor activity. Involved in actin filament organization and post-Golgi vesicle-mediated transport. Located in several cellular components, including actin filament; endosome; and perinuclear region of cytoplasm. Colocalizes with trans-Golgi network membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 2-191390304-G-A is Benign according to our data. Variant chr2-191390304-G-A is described in ClinVar as [Benign]. Clinvar id is 775797.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.928 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0526 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO1B	NM_001130158.3	c.1794G>A	p.Pro598=	synonymous_variant	18/31	ENST00000392318.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO1B	ENST00000392318.8	c.1794G>A	p.Pro598=	synonymous_variant	18/31	1	NM_001130158.3	P1
MYO1B	ENST00000304164.8	c.1794G>A	p.Pro598=	synonymous_variant	18/31	1		P1
MYO1B	ENST00000339514.8	c.1794G>A	p.Pro598=	synonymous_variant	18/29	1
MYO1B	ENST00000392316.5	c.1794G>A	p.Pro598=	synonymous_variant	17/29	5

Frequencies

GnomAD3 genomes AF: 0.0157 AC: 2393 AN: 152194 Hom.: 61 Cov.: 33

Gnomad AFR AF: 0.0543

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00680

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.0129

GnomAD3 exomes AF: 0.00411 AC: 1031 AN: 251108 Hom.: 17 AF XY: 0.00293 AC XY: 397 AN XY: 135712

Gnomad AFR exome AF: 0.0552

Gnomad AMR exome AF: 0.00313

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000654

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000114

Gnomad OTH exome AF: 0.00163

GnomAD4 exome AF: 0.00162 AC: 2363 AN: 1460918 Hom.: 55 Cov.: 31 AF XY: 0.00135 AC XY: 983 AN XY: 726628

Gnomad4 AFR exome AF: 0.0564

Gnomad4 AMR exome AF: 0.00349

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000128

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.0000756

Gnomad4 OTH exome AF: 0.00353

GnomAD4 genome AF: 0.0158 AC: 2405 AN: 152312 Hom.: 62 Cov.: 33 AF XY: 0.0156 AC XY: 1160 AN XY: 74486

Gnomad4 AFR AF: 0.0545

Gnomad4 AMR AF: 0.00680

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000147

Gnomad4 OTH AF: 0.0128

Alfa AF: 0.00523 Hom.: 8

Bravo AF: 0.0184

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
Cadd	Benign	1.4
Dann	Benign	0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs73984118; hg19: chr2-192255030;