rs4853578

chr2-191297215-G-Achr2-191297215-G-C

Variant summary

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

The NM_001130158.3(MYO1B):c.251+989G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.53 in 151,984 control chromosomes in the GnomAD database, including 22,080 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 0.53 (22080 hom., cov: 32)
• Consequence: MYO1B NM_001130158.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.10

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.637 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO1B	NM_001130158.3	c.251+989G>A		intron_variant		ENST00000392318.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO1B	ENST00000392318.8	c.251+989G>A		intron_variant		1	NM_001130158.3	P1

Frequencies

GnomAD3 genomes AF: 0.530 AC: 80482 AN: 151866 Hom.: 22066 Cov.: 32

Gnomad AFR AF: 0.371

Gnomad AMI AF: 0.691

Gnomad AMR AF: 0.573

Gnomad ASJ AF: 0.509

Gnomad EAS AF: 0.655

Gnomad SAS AF: 0.494

Gnomad FIN AF: 0.662

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.589

Gnomad OTH AF: 0.511

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

GnomAD4 genome AF: 0.530 AC: 80530 AN: 151984 Hom.: 22080 Cov.: 32 AF XY: 0.535 AC XY: 39761 AN XY: 74290

Gnomad4 AFR AF: 0.371

Gnomad4 AMR AF: 0.573

Gnomad4 ASJ AF: 0.509

Gnomad4 EAS AF: 0.656

Gnomad4 SAS AF: 0.493

Gnomad4 FIN AF: 0.662

Gnomad4 NFE AF: 0.589

Gnomad4 OTH AF: 0.509

Alfa AF: 0.564 Hom.: 4197

Bravo AF: 0.519

Asia WGS AF: 0.560 AC: 1947 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.26
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: rs4853578; hg19: chr2-192161941;