rs4853578

Variant names:

• chr2-191297215-G-A
• rs4853578
• NM_001130158.3:c.251+989G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-191297215-G-A
• chr2-191297215-G-C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001130158.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO1B	NM_001130158.3	MANE Select	c.251+989G>A		intron	N/A	NP_001123630.1	O43795-1
	MYO1B	NM_001161819.3		c.251+989G>A		intron	N/A	NP_001155291.1	B0I1S9
	MYO1B	NM_001330237.2		c.251+989G>A		intron	N/A	NP_001317166.1	E9PDF6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO1B	ENST00000392318.8	TSL:1 MANE Select	c.251+989G>A		intron	N/A	ENSP00000376132.3	O43795-1
	MYO1B	ENST00000304164.8	TSL:1	c.251+989G>A		intron	N/A	ENSP00000306382.4	O43795-1
	MYO1B	ENST00000339514.8	TSL:1	c.251+989G>A		intron	N/A	ENSP00000341903.4	O43795-2

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

African (AFR) AF: 0.371 AC: 15375 AN: 41418

American (AMR) AF: 0.573 AC: 8750 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.509 AC: 1766 AN: 3470

East Asian (EAS) AF: 0.656 AC: 3391 AN: 5172

South Asian (SAS) AF: 0.493 AC: 2378 AN: 4822

European-Finnish (FIN) AF: 0.662 AC: 6985 AN: 10550

Middle Eastern (MID) AF: 0.456 AC: 134 AN: 294

European-Non Finnish (NFE) AF: 0.589 AC: 40045 AN: 67970

Other (OTH) AF: 0.509 AC: 1077 AN: 2114

Alfa AF: 0.558 Hom.: 4247

Bravo AF: 0.519

Asia WGS AF: 0.560 AC: 1947 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.26
DANN	Benign	0.75
PhyloP100		-2.1
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: rs4853578; hg19: chr2-192161941;