18-49849562-C-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001080467.3(MYO5B):c.4315+5G>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.455 in 1,599,336 control chromosomes in the GnomAD database, including 171,694 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.44 ( 15407 hom., cov: 32)

Exomes 𝑓: 0.46 ( 156287 hom. )

Consequence

MYO5B
NM_001080467.3 splice_region, intron

Scores

Splicing: ADA: 0.09528

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -4.32

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 18-49849562-C-G is Benign according to our data. Variant chr18-49849562-C-G is described in ClinVar as [Benign]. Clinvar id is 327014.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-49849562-C-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.487 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO5B	NM_001080467.3 link	c.4315+5G>C		splice_region_variant, intron_variant	Intron 32 of 39	ENST00000285039.12	NP_001073936.1	Q9ULV0-1Q7Z7A5
SNHG22	NR_117096.1 link	n.193-75C>G		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO5B	ENST00000285039.12 link	c.4315+5G>C		splice_region_variant, intron_variant	Intron 32 of 39	1	NM_001080467.3	ENSP00000285039.6		Q9ULV0-1

Frequencies

GnomAD3 genomes

AF:

0.442

AC:

67179

AN:

151942

Hom.:

15410

Cov.:

show subpopulations

Gnomad AFR

AF:

0.437

Gnomad AMI

AF:

0.664

Gnomad AMR

AF:

0.373

Gnomad ASJ

AF:

0.554

Gnomad EAS

AF:

0.116

Gnomad SAS

AF:

0.314

Gnomad FIN

AF:

0.396

Gnomad MID

AF:

0.541

Gnomad NFE

AF:

0.492

Gnomad OTH

AF:

0.478

GnomAD3 exomes

AF:

0.402

AC:

100225

AN:

249532

Hom.:

22136

AF XY:

0.409

AC XY:

55416

AN XY:

135386

show subpopulations

Gnomad AFR exome

AF:

0.440

Gnomad AMR exome

AF:

0.256

Gnomad ASJ exome

AF:

0.549

Gnomad EAS exome

AF:

0.114

Gnomad SAS exome

AF:

0.336

Gnomad FIN exome

AF:

0.392

Gnomad NFE exome

AF:

0.491

Gnomad OTH exome

AF:

0.436

GnomAD4 exome

AF:

0.456

AC:

660342

AN:

1447276

Hom.:

156287

Cov.:

AF XY:

0.455

AC XY:

327787

AN XY:

720826

show subpopulations

Gnomad4 AFR exome

AF:

0.442

Gnomad4 AMR exome

AF:

0.270

Gnomad4 ASJ exome

AF:

0.553

Gnomad4 EAS exome

AF:

0.122

Gnomad4 SAS exome

AF:

0.334

Gnomad4 FIN exome

AF:

0.390

Gnomad4 NFE exome

AF:

0.487

Gnomad4 OTH exome

AF:

0.443

GnomAD4 genome

AF:

0.442

AC:

67189

AN:

152060

Hom.:

15407

Cov.:

AF XY:

0.434

AC XY:

32271

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.437

Gnomad4 AMR

AF:

0.372

Gnomad4 ASJ

AF:

0.554

Gnomad4 EAS

AF:

0.116

Gnomad4 SAS

AF:

0.314

Gnomad4 FIN

AF:

0.396

Gnomad4 NFE

AF:

0.492

Gnomad4 OTH

AF:

0.474

Alfa

AF:

0.450

Hom.:

4598

Bravo

AF:

0.440

Asia WGS

AF:

0.260

AC:

905

AN:

3478

EpiCase

AF:

0.502

EpiControl

AF:

0.510

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Congenital microvillous atrophy

Benign:4

Sep 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oct 09, 2014

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.037

DANN

Benign

0.46

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.095

dbscSNV1_RF

Benign

0.11

SpliceAI score (max)

0.16

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