2-191296213-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BA1

The NM_001130158.3(MYO1B):c.238C>T(p.Leu80=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00276 in 1,604,322 control chromosomes in the GnomAD database, including 106 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.015 (64 hom., cov: 33)
  • Exomes 𝑓: 0.0015 (42 hom.)
• Consequence: MYO1B NM_001130158.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.99

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.27).
• BP6: Variant 2-191296213-C-T is Benign according to our data. Variant chr2-191296213-C-T is described in ClinVar as [Benign]. Clinvar id is 783992.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.99 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0507 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO1B	NM_001130158.3	c.238C>T	p.Leu80=	synonymous_variant	3/31	ENST00000392318.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO1B	ENST00000392318.8	c.238C>T	p.Leu80=	synonymous_variant	3/31	1	NM_001130158.3	P1

Frequencies

GnomAD3 genomes AF: 0.0150 AC: 2287 AN: 152128 Hom.: 64 Cov.: 33

Gnomad AFR AF: 0.0526

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00478

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.0139

GnomAD3 exomes AF: 0.00368 AC: 917 AN: 248950 Hom.: 15 AF XY: 0.00268 AC XY: 361 AN XY: 134618

Gnomad AFR exome AF: 0.0514

Gnomad AMR exome AF: 0.00183

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000132

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000708

Gnomad OTH exome AF: 0.00182

GnomAD4 exome AF: 0.00147 AC: 2133 AN: 1452076 Hom.: 42 Cov.: 29 AF XY: 0.00125 AC XY: 901 AN XY: 722936

Gnomad4 AFR exome AF: 0.0537

Gnomad4 AMR exome AF: 0.00205

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000175

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000344

Gnomad4 OTH exome AF: 0.00323

GnomAD4 genome AF: 0.0150 AC: 2290 AN: 152246 Hom.: 64 Cov.: 33 AF XY: 0.0142 AC XY: 1053 AN XY: 74416

Gnomad4 AFR AF: 0.0525

Gnomad4 AMR AF: 0.00477

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.0137

Alfa AF: 0.00659 Hom.: 14

Bravo AF: 0.0169

Asia WGS AF: 0.00260 AC: 10 AN: 3474

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

Jan 08, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
Cadd	Benign	10
Dann	Benign	0.81

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: rs16833579; hg19: chr2-192160939;