rs1942418

chr18-49856873-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001080467.3(MYO5B):c.3962G>A(p.Gly1321Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0723 in 1,613,512 control chromosomes in the GnomAD database, including 9,225 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.079 (955 hom., cov: 33)
  • Exomes 𝑓: 0.072 (8270 hom.)
• Consequence: MYO5B NM_001080467.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 5.59

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0016974807).
• BP6: Variant 18-49856873-C-T is Benign according to our data. Variant chr18-49856873-C-T is described in ClinVar as [Benign]. Clinvar id is 327017.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-49856873-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.284 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO5B	NM_001080467.3	c.3962G>A	p.Gly1321Glu	missense_variant	30/40	ENST00000285039.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO5B	ENST00000285039.12	c.3962G>A	p.Gly1321Glu	missense_variant	30/40	1	NM_001080467.3	P1

Frequencies

GnomAD3 genomes AF: 0.0793 AC: 12062 AN: 152190 Hom.: 946 Cov.: 33

Gnomad AFR AF: 0.0547

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.229

Gnomad ASJ AF: 0.0458

Gnomad EAS AF: 0.297

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.0562

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0478

Gnomad OTH AF: 0.0894

GnomAD3 exomes AF: 0.121 AC: 30124 AN: 249452 Hom.: 3953 AF XY: 0.108 AC XY: 14647 AN XY: 135344

Gnomad AFR exome AF: 0.0548

Gnomad AMR exome AF: 0.384

Gnomad ASJ exome AF: 0.0448

Gnomad EAS exome AF: 0.293

Gnomad SAS exome AF: 0.102

Gnomad FIN exome AF: 0.0578

Gnomad NFE exome AF: 0.0478

Gnomad OTH exome AF: 0.0933

GnomAD4 exome AF: 0.0715 AC: 104540 AN: 1461204 Hom.: 8270 Cov.: 31 AF XY: 0.0710 AC XY: 51598 AN XY: 726946

Gnomad4 AFR exome AF: 0.0553

Gnomad4 AMR exome AF: 0.365

Gnomad4 ASJ exome AF: 0.0432

Gnomad4 EAS exome AF: 0.361

Gnomad4 SAS exome AF: 0.103

Gnomad4 FIN exome AF: 0.0569

Gnomad4 NFE exome AF: 0.0485

Gnomad4 OTH exome AF: 0.0755

GnomAD4 genome AF: 0.0794 AC: 12094 AN: 152308 Hom.: 955 Cov.: 33 AF XY: 0.0840 AC XY: 6257 AN XY: 74464

Gnomad4 AFR AF: 0.0547

Gnomad4 AMR AF: 0.230

Gnomad4 ASJ AF: 0.0458

Gnomad4 EAS AF: 0.296

Gnomad4 SAS AF: 0.113

Gnomad4 FIN AF: 0.0562

Gnomad4 NFE AF: 0.0478

Gnomad4 OTH AF: 0.0903

Alfa AF: 0.0601 Hom.: 1349

Bravo AF: 0.0957

TwinsUK AF: 0.0499 AC: 185

ALSPAC AF: 0.0519 AC: 200

ESP6500AA AF: 0.0482 AC: 184

ESP6500EA AF: 0.0517 AC: 427

ExAC AF: 0.109 AC: 13137

Asia WGS AF: 0.177 AC: 613 AN: 3478

EpiCase AF: 0.0492

EpiControl AF: 0.0483

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

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	- -

Congenital microvillous atrophy Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 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. -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.56
Cadd	Uncertain	23
Dann	Benign	0.96
DEOGEN2	Benign	0.030	T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.025
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.58	T
MetaRNN	Benign	0.0017	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.6	L
MutationTaster	Benign	0.0000022	P;P
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	0.43	N
REVEL	Benign	0.081
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.049	B
Vest4		0.37
MPC		0.71
ClinPred		0.024	T
GERP RS		5.3
Varity_R		0.19
gMVP		0.61

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: rs1942418; hg19: chr18-47383243; COSMIC: COSV53213017;