18-49962255-A-G

Variant names:

• chr18-49962255-A-G
• rs17715416
• NM_001080467.3:c.1545+11T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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 Gene-Disease associations (from GenCC):

• microvillus inclusion disease

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae)
• cholestasis, progressive familial intrahepatic, 10

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• progressive familial intrahepatic cholestasis type 1

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 327063.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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 rank	MANE	Protein	UniProt
MYO5B	NM_001080467.3	c.1545+11T>C		intron_variant	Intron 12 of 39	ENST00000285039.12	NP_001073936.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO5B	ENST00000285039.12	c.1545+11T>C		intron_variant	Intron 12 of 39	1	NM_001080467.3	ENSP00000285039.6
MYO5B	ENST00000697219.1	c.1341+11T>C		intron_variant	Intron 10 of 37			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

GnomAD2 exomes AF: 0.387 AC: 96556 AN: 249440 AF XY: 0.395

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 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

African (AFR) AF: 0.191 AC: 6395 AN: 33476

American (AMR) AF: 0.476 AC: 21288 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.355 AC: 9271 AN: 26128

East Asian (EAS) AF: 0.270 AC: 10728 AN: 39690

South Asian (SAS) AF: 0.521 AC: 44922 AN: 86242

European-Finnish (FIN) AF: 0.320 AC: 17081 AN: 53418

Middle Eastern (MID) AF: 0.440 AC: 2536 AN: 5766

European-Non Finnish (NFE) AF: 0.383 AC: 425620 AN: 1111564

Other (OTH) AF: 0.371 AC: 22407 AN: 60378

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

African (AFR) AF: 0.203 AC: 8436 AN: 41518

American (AMR) AF: 0.415 AC: 6343 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.355 AC: 1231 AN: 3470

East Asian (EAS) AF: 0.259 AC: 1341 AN: 5174

South Asian (SAS) AF: 0.516 AC: 2480 AN: 4806

European-Finnish (FIN) AF: 0.322 AC: 3403 AN: 10566

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.393 AC: 26681 AN: 67976

Other (OTH) AF: 0.344 AC: 727 AN: 2116

Alfa AF: 0.336 Hom.: 2721

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

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

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 19, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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	-0.80
CADD	Benign	4.0
DANN	Benign	0.70
PhyloP100		-0.022
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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