rs3841750

chr18-49879055-T-TGAG

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 1P and 16B. PM4_Supporting BP6_Very_Strong BA1

The NM_001080467.3(MYO5B):c.3165_3166insCTC(p.Leu1055dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 1,613,342 control chromosomes in the GnomAD database, including 78,462 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.32 (8240 hom., cov: 0)
  • Exomes 𝑓: 0.30 (70222 hom.)
• Consequence: MYO5B NM_001080467.3 inframe_insertion
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts P:1 B:5
• Conservation: PhyloP100: -0.226

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 -15 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_001080467.3. Strenght limited to Supporting due to length of the change: 1aa.
• BP6: Variant 18-49879055-T-TGAG is Benign according to our data. Variant chr18-49879055-T-TGAG is described in ClinVar as [Benign]. Clinvar id is 327031.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.526 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO5B	NM_001080467.3	c.3165_3166insCTC	p.Leu1055dup	inframe_insertion	24/40	ENST00000285039.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO5B	ENST00000285039.12	c.3165_3166insCTC	p.Leu1055dup	inframe_insertion	24/40	1	NM_001080467.3	P1

Frequencies

GnomAD3 genomes AF: 0.324 AC: 49135 AN: 151762 Hom.: 8235 Cov.: 0

Gnomad AFR AF: 0.363

Gnomad AMI AF: 0.273

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.542

Gnomad SAS AF: 0.501

Gnomad FIN AF: 0.365

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.279

Gnomad OTH AF: 0.291

GnomAD3 exomes AF: 0.340 AC: 84825 AN: 249362 Hom.: 15532 AF XY: 0.346 AC XY: 46763 AN XY: 135288

Gnomad AFR exome AF: 0.359

Gnomad AMR exome AF: 0.286

Gnomad ASJ exome AF: 0.281

Gnomad EAS exome AF: 0.557

Gnomad SAS exome AF: 0.495

Gnomad FIN exome AF: 0.364

Gnomad NFE exome AF: 0.280

Gnomad OTH exome AF: 0.316

GnomAD4 exome AF: 0.302 AC: 441199 AN: 1461462 Hom.: 70222 Cov.: 34 AF XY: 0.308 AC XY: 223571 AN XY: 727058

Gnomad4 AFR exome AF: 0.363

Gnomad4 AMR exome AF: 0.286

Gnomad4 ASJ exome AF: 0.278

Gnomad4 EAS exome AF: 0.496

Gnomad4 SAS exome AF: 0.493

Gnomad4 FIN exome AF: 0.363

Gnomad4 NFE exome AF: 0.276

Gnomad4 OTH exome AF: 0.314

GnomAD4 genome AF: 0.324 AC: 49182 AN: 151880 Hom.: 8240 Cov.: 0 AF XY: 0.331 AC XY: 24575 AN XY: 74234

Gnomad4 AFR AF: 0.363

Gnomad4 AMR AF: 0.282

Gnomad4 ASJ AF: 0.263

Gnomad4 EAS AF: 0.542

Gnomad4 SAS AF: 0.501

Gnomad4 FIN AF: 0.365

Gnomad4 NFE AF: 0.279

Gnomad4 OTH AF: 0.293

Alfa AF: 0.296 Hom.: 4046

Bravo AF: 0.315

Asia WGS AF: 0.484 AC: 1683 AN: 3478

EpiCase AF: 0.272

EpiControl AF: 0.270

ClinVar

Significance: Benign

Submissions summary: Pathogenic:1 Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Congenital microvillous atrophy Pathogenic:1 Benign:1

Pathogenic, no assertion criteria provided	literature only	OMIM	May 20, 2022	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 05, 2021	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	This variant is associated with the following publications: (PMID: 24014347, 28492530, 25111220) -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

- -

Diarrhea with Microvillus Atrophy Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs397841722; hg19: chr18-47405425;