rs555879

chr18-49826163-G-A

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.*308C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.54 in 366,126 control chromosomes in the GnomAD database, including 53,808 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.54 (22089 hom., cov: 33)
  • Exomes 𝑓: 0.54 (31719 hom.)
• Consequence: MYO5B NM_001080467.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.246

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]

SNHG22 (HGNC:50285): (small nucleolar RNA host gene 22)

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 18-49826163-G-A is Benign according to our data. Variant chr18-49826163-G-A is described in ClinVar as [Benign]. Clinvar id is 326990.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.601 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO5B	NM_001080467.3	c.*308C>T		3_prime_UTR_variant	40/40	ENST00000285039.12
SNHG22	NR_117096.1	n.40+12101G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO5B	ENST00000285039.12	c.*308C>T		3_prime_UTR_variant	40/40	1	NM_001080467.3	P1
SNHG22	ENST00000589499.1	n.40+12101G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.538 AC: 81647 AN: 151884 Hom.: 22074 Cov.: 33

Gnomad AFR AF: 0.526

Gnomad AMI AF: 0.669

Gnomad AMR AF: 0.611

Gnomad ASJ AF: 0.620

Gnomad EAS AF: 0.415

Gnomad SAS AF: 0.541

Gnomad FIN AF: 0.463

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.541

Gnomad OTH AF: 0.577

GnomAD4 exome AF: 0.541 AC: 115827 AN: 214124 Hom.: 31719 Cov.: 2 AF XY: 0.542 AC XY: 62313 AN XY: 114920

Gnomad4 AFR exome AF: 0.535

Gnomad4 AMR exome AF: 0.630

Gnomad4 ASJ exome AF: 0.620

Gnomad4 EAS exome AF: 0.453

Gnomad4 SAS exome AF: 0.550

Gnomad4 FIN exome AF: 0.456

Gnomad4 NFE exome AF: 0.543

Gnomad4 OTH exome AF: 0.537

GnomAD4 genome AF: 0.538 AC: 81711 AN: 152002 Hom.: 22089 Cov.: 33 AF XY: 0.538 AC XY: 39936 AN XY: 74276

Gnomad4 AFR AF: 0.526

Gnomad4 AMR AF: 0.611

Gnomad4 ASJ AF: 0.620

Gnomad4 EAS AF: 0.414

Gnomad4 SAS AF: 0.542

Gnomad4 FIN AF: 0.463

Gnomad4 NFE AF: 0.541

Gnomad4 OTH AF: 0.573

Alfa AF: 0.538 Hom.: 2689

Bravo AF: 0.549

Asia WGS AF: 0.505 AC: 1755 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Congenital microvillous atrophy Benign:1

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:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	4.9
Dann	Benign	0.54

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: rs555879; hg19: chr18-47352533;