18-49962255-A-G

Position:

• chr18-49962255-A-G

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.1545+11T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 1,613,492 control chromosomes in the GnomAD database, including 119,175 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.34 (9231 hom., cov: 32)
  • Exomes 𝑓: 0.38 (109944 hom.)
• Consequence: MYO5B NM_001080467.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.0220

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=-0.8).
• BP6: Variant 18-49962255-A-G is Benign according to our data. Variant chr18-49962255-A-G is described in ClinVar as [Benign]. Clinvar id is 327063.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-49962255-A-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.499 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO5B	NM_001080467.3	c.1545+11T>C		intron_variant		ENST00000285039.12	NP_001073936.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYO5B	ENST00000285039.12	c.1545+11T>C		intron_variant		1	NM_001080467.3	ENSP00000285039.6
MYO5B	ENST00000697219.1	c.1341+11T>C		intron_variant				ENSP00000513188.1

Frequencies

GnomAD3 genomes AF: 0.335 AC: 50978 AN: 151988 Hom.: 9229 Cov.: 32

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.262

Gnomad AMR AF: 0.415

Gnomad ASJ AF: 0.355

Gnomad EAS AF: 0.259

Gnomad SAS AF: 0.516

Gnomad FIN AF: 0.322

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.393

Gnomad OTH AF: 0.345

GnomAD3 exomes AF: 0.387 AC: 96556 AN: 249440 Hom.: 19901 AF XY: 0.395 AC XY: 53393 AN XY: 135330

Gnomad AFR exome AF: 0.192

Gnomad AMR exome AF: 0.481

Gnomad ASJ exome AF: 0.362

Gnomad EAS exome AF: 0.253

Gnomad SAS exome AF: 0.519

Gnomad FIN exome AF: 0.319

Gnomad NFE exome AF: 0.386

Gnomad OTH exome AF: 0.379

GnomAD4 exome AF: 0.383 AC: 560248 AN: 1461386 Hom.: 109944 Cov.: 41 AF XY: 0.389 AC XY: 282536 AN XY: 727022

Gnomad4 AFR exome AF: 0.191

Gnomad4 AMR exome AF: 0.476

Gnomad4 ASJ exome AF: 0.355

Gnomad4 EAS exome AF: 0.270

Gnomad4 SAS exome AF: 0.521

Gnomad4 FIN exome AF: 0.320

Gnomad4 NFE exome AF: 0.383

Gnomad4 OTH exome AF: 0.371

GnomAD4 genome AF: 0.335 AC: 50998 AN: 152106 Hom.: 9231 Cov.: 32 AF XY: 0.339 AC XY: 25181 AN XY: 74344

Gnomad4 AFR AF: 0.203

Gnomad4 AMR AF: 0.415

Gnomad4 ASJ AF: 0.355

Gnomad4 EAS AF: 0.259

Gnomad4 SAS AF: 0.516

Gnomad4 FIN AF: 0.322

Gnomad4 NFE AF: 0.393

Gnomad4 OTH AF: 0.344

Alfa AF: 0.338 Hom.: 2699

Bravo AF: 0.330

Asia WGS AF: 0.363 AC: 1263 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Congenital microvillous atrophy Benign:3

Benign, criteria provided, single submitter	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	Oct 09, 2014	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
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 provided Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	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	-0.80
CADD	Benign	4.0
DANN	Benign	0.70

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: rs17715416; hg19: chr18-47488625; COSMIC: COSV53214173;