2-191379667-A-G

Variant summary

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

The NM_001130158.3(MYO1B):c.1186-1795A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.785 in 152,092 control chromosomes in the GnomAD database, including 52,583 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 0.79 (52583 hom., cov: 32)
• Consequence: MYO1B NM_001130158.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.480

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.97 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO1B	NM_001130158.3	c.1186-1795A>G		intron_variant		ENST00000392318.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO1B	ENST00000392318.8	c.1186-1795A>G		intron_variant		1	NM_001130158.3	P1

Frequencies

GnomAD3 genomes AF: 0.786 AC: 119414 AN: 151974 Hom.: 52574 Cov.: 32

Gnomad AFR AF: 0.353

Gnomad AMI AF: 0.999

Gnomad AMR AF: 0.820

Gnomad ASJ AF: 0.897

Gnomad EAS AF: 0.946

Gnomad SAS AF: 0.953

Gnomad FIN AF: 0.982

Gnomad MID AF: 0.864

Gnomad NFE AF: 0.976

Gnomad OTH AF: 0.810

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

GnomAD4 genome AF: 0.785 AC: 119441 AN: 152092 Hom.: 52583 Cov.: 32 AF XY: 0.789 AC XY: 58650 AN XY: 74358

Gnomad4 AFR AF: 0.353

Gnomad4 AMR AF: 0.820

Gnomad4 ASJ AF: 0.897

Gnomad4 EAS AF: 0.946

Gnomad4 SAS AF: 0.953

Gnomad4 FIN AF: 0.982

Gnomad4 NFE AF: 0.976

Gnomad4 OTH AF: 0.812

Alfa AF: 0.900 Hom.: 31038

Bravo AF: 0.753

Asia WGS AF: 0.911 AC: 3167 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	3.3
Dann	Benign	0.84

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: rs1517835; hg19: chr2-192244393;