Variant 18-49843388-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001080467.3(MYO5B):c.4464G>A(p.Leu1488=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0731 in 1,613,966 control chromosomes in the GnomAD database, including 9,304 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.079 ( 950 hom., cov: 33)

Exomes 𝑓: 0.072 ( 8354 hom. )

Consequence

MYO5B
NM_001080467.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.750

Variant links:

Genes affected

MYO5B (HGNC:7603): (myosin VB) The protein encoded by this gene, together with other proteins, may be involved in plasma membrane recycling. Mutations in this gene are associated with microvillous inclusion disease. [provided by RefSeq, Sep 2009]

MYO5B links:

SNHG22 (HGNC:50285): (small nucleolar RNA host gene 22)

SNHG22 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 18-49843388-C-T is Benign according to our data. Variant chr18-49843388-C-T is described in ClinVar as [Benign]. Clinvar id is 327010.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-49843388-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.75 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.28 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO5B	NM_001080467.3 linkuse as main transcript	c.4464G>A	p.Leu1488=	synonymous_variant	34/40	ENST00000285039.12
SNHG22	NR_117096.1 linkuse as main transcript	n.192+2963C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO5B	ENST00000285039.12 linkuse as main transcript	c.4464G>A	p.Leu1488=	synonymous_variant	34/40	1	NM_001080467.3	P1	Q9ULV0-1
SNHG22	ENST00000589499.1 linkuse as main transcript	n.192+2963C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0790

AC:

12019

AN:

152044

Hom.:

941

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0528

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.228

Gnomad ASJ

AF:

0.0383

Gnomad EAS

AF:

0.292

Gnomad SAS

AF:

0.120

Gnomad FIN

AF:

0.0647

Gnomad MID

AF:

0.0573

Gnomad NFE

AF:

0.0477

Gnomad OTH

AF:

0.0876

GnomAD3 exomes

AF:

0.122

AC:

30529

AN:

249252

Hom.:

4010

AF XY:

0.111

AC XY:

14975

AN XY:

135260

show subpopulations

Gnomad AFR exome

AF:

0.0534

Gnomad AMR exome

AF:

0.383

Gnomad ASJ exome

AF:

0.0372

Gnomad EAS exome

AF:

0.287

Gnomad SAS exome

AF:

0.114

Gnomad FIN exome

AF:

0.0661

Gnomad NFE exome

AF:

0.0481

Gnomad OTH exome

AF:

0.0949

GnomAD4 exome

AF:

0.0724

AC:

105856

AN:

1461804

Hom.:

8354

Cov.:

AF XY:

0.0722

AC XY:

52529

AN XY:

727212

show subpopulations

Gnomad4 AFR exome

AF:

0.0542

Gnomad4 AMR exome

AF:

0.364

Gnomad4 ASJ exome

AF:

0.0364

Gnomad4 EAS exome

AF:

0.357

Gnomad4 SAS exome

AF:

0.115

Gnomad4 FIN exome

AF:

0.0647

Gnomad4 NFE exome

AF:

0.0487

Gnomad4 OTH exome

AF:

0.0768

GnomAD4 genome

AF:

0.0792

AC:

12049

AN:

152162

Hom.:

950

Cov.:

AF XY:

0.0840

AC XY:

6250

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.0528

Gnomad4 AMR

AF:

0.229

Gnomad4 ASJ

AF:

0.0383

Gnomad4 EAS

AF:

0.292

Gnomad4 SAS

AF:

0.122

Gnomad4 FIN

AF:

0.0647

Gnomad4 NFE

AF:

0.0477

Gnomad4 OTH

AF:

0.0882

Alfa

AF:

0.0616

Hom.:

825

Bravo

AF:

0.0945

Asia WGS

AF:

0.187

AC:

648

AN:

3478

EpiCase

AF:

0.0488

EpiControl

AF:

0.0480

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 09, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

- -

Congenital microvillous atrophy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

9.6

DANN

Benign

0.59

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over