rs2276176

Variant names:

• chr18-49878934-A-G
• rs2276176
• NM_001080467.3:c.3276+11T>C

Your query was ambiguous. Multiple possible variants found:

• chr18-49878934-A-G
• chr18-49878934-A-T

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.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:6
• Conservation: PhyloP100: -0.0160
• Publications: 8 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=-0.9).
• BP6: Variant 18-49878934-A-G is Benign according to our data. Variant chr18-49878934-A-G is described in ClinVar as Benign. ClinVar VariationId is 327030.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.406 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO5B	NM_001080467.3	c.3276+11T>C		intron_variant	Intron 24 of 39	ENST00000285039.12	NP_001073936.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO5B	ENST00000285039.12	c.3276+11T>C		intron_variant	Intron 24 of 39	1	NM_001080467.3	ENSP00000285039.6

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

GnomAD2 exomes AF: 0.253 AC: 62941 AN: 249086 AF XY: 0.254

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 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

African (AFR) AF: 0.235 AC: 7883 AN: 33474

American (AMR) AF: 0.261 AC: 11651 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.223 AC: 5835 AN: 26132

East Asian (EAS) AF: 0.383 AC: 15187 AN: 39682

South Asian (SAS) AF: 0.339 AC: 29278 AN: 86240

European-Finnish (FIN) AF: 0.257 AC: 13720 AN: 53346

Middle Eastern (MID) AF: 0.235 AC: 1354 AN: 5756

European-Non Finnish (NFE) AF: 0.197 AC: 218447 AN: 1111650

Other (OTH) AF: 0.230 AC: 13891 AN: 60358

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

African (AFR) AF: 0.241 AC: 9971 AN: 41324

American (AMR) AF: 0.244 AC: 3713 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.214 AC: 740 AN: 3466

East Asian (EAS) AF: 0.421 AC: 2166 AN: 5142

South Asian (SAS) AF: 0.343 AC: 1643 AN: 4796

European-Finnish (FIN) AF: 0.259 AC: 2725 AN: 10504

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.199 AC: 13492 AN: 67910

Other (OTH) AF: 0.227 AC: 477 AN: 2102

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:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Congenital microvillous atrophy Benign:2

Sep 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 12, 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. -

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	-0.90
CADD	Benign	6.9
DANN	Benign	0.53
PhyloP100		-0.016
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs2276176; hg19: chr18-47405304;