rs2276176

chr18-49878934-A-Gchr18-49878934-A-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.3276+11T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 1,613,030 control chromosomes in the GnomAD database, including 40,786 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.23 (4204 hom., cov: 32)
  • Exomes 𝑓: 0.22 (36582 hom.)
• Consequence: MYO5B NM_001080467.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.0160

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 (BayesDel_noAF=-0.9).
• BP6: Variant 18-49878934-A-G is Benign according to our data. Variant chr18-49878934-A-G is described in ClinVar as [Benign]. Clinvar id is 327030.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-49878934-A-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.406 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO5B	NM_001080467.3	c.3276+11T>C		intron_variant		ENST00000285039.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO5B	ENST00000285039.12	c.3276+11T>C		intron_variant		1	NM_001080467.3	P1

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35133 AN: 151574 Hom.: 4200 Cov.: 32

Gnomad AFR AF: 0.241

Gnomad AMI AF: 0.195

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.214

Gnomad EAS AF: 0.421

Gnomad SAS AF: 0.342

Gnomad FIN AF: 0.259

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.199

Gnomad OTH AF: 0.225

GnomAD3 exomes AF: 0.253 AC: 62941 AN: 249086 Hom.: 8666 AF XY: 0.254 AC XY: 34306 AN XY: 135168

Gnomad AFR exome AF: 0.235

Gnomad AMR exome AF: 0.262

Gnomad ASJ exome AF: 0.224

Gnomad EAS exome AF: 0.435

Gnomad SAS exome AF: 0.344

Gnomad FIN exome AF: 0.258

Gnomad NFE exome AF: 0.201

Gnomad OTH exome AF: 0.244

GnomAD4 exome AF: 0.217 AC: 317246 AN: 1461338 Hom.: 36582 Cov.: 34 AF XY: 0.220 AC XY: 160194 AN XY: 726998

Gnomad4 AFR exome AF: 0.235

Gnomad4 AMR exome AF: 0.261

Gnomad4 ASJ exome AF: 0.223

Gnomad4 EAS exome AF: 0.383

Gnomad4 SAS exome AF: 0.339

Gnomad4 FIN exome AF: 0.257

Gnomad4 NFE exome AF: 0.197

Gnomad4 OTH exome AF: 0.230

GnomAD4 genome AF: 0.232 AC: 35168 AN: 151692 Hom.: 4204 Cov.: 32 AF XY: 0.238 AC XY: 17630 AN XY: 74120

Gnomad4 AFR AF: 0.241

Gnomad4 AMR AF: 0.244

Gnomad4 ASJ AF: 0.214

Gnomad4 EAS AF: 0.421

Gnomad4 SAS AF: 0.343

Gnomad4 FIN AF: 0.259

Gnomad4 NFE AF: 0.199

Gnomad4 OTH AF: 0.227

Alfa AF: 0.163 Hom.: 472

Bravo AF: 0.230

Asia WGS AF: 0.362 AC: 1258 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Congenital microvillous atrophy Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 05, 2021	- -
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. -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -

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
BayesDel_noAF	Benign	-0.90
Cadd	Benign	6.9
Dann	Benign	0.53
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2276176; hg19: chr18-47405304;