rs17727982

chr18-49909180-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001080467.3(MYO5B):c.2203-2550T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 152,282 control chromosomes in the GnomAD database, including 1,424 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.12 (1424 hom., cov: 33)
• Consequence: MYO5B NM_001080467.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.12

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.279 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO5B	NM_001080467.3	c.2203-2550T>C		intron_variant		ENST00000285039.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO5B	ENST00000285039.12	c.2203-2550T>C		intron_variant		1	NM_001080467.3	P1
MYO5B	ENST00000697219.1	c.2000-2550T>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18833 AN: 152164 Hom.: 1426 Cov.: 33

Gnomad AFR AF: 0.0457

Gnomad AMI AF: 0.147

Gnomad AMR AF: 0.162

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.292

Gnomad SAS AF: 0.170

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.123

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.124 AC: 18836 AN: 152282 Hom.: 1424 Cov.: 33 AF XY: 0.128 AC XY: 9509 AN XY: 74450

Gnomad4 AFR AF: 0.0456

Gnomad4 AMR AF: 0.162

Gnomad4 ASJ AF: 0.107

Gnomad4 EAS AF: 0.291

Gnomad4 SAS AF: 0.170

Gnomad4 FIN AF: 0.183

Gnomad4 NFE AF: 0.138

Gnomad4 OTH AF: 0.127

Alfa AF: 0.133 Hom.: 258

Bravo AF: 0.119

Asia WGS AF: 0.202 AC: 702 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.45
Dann	Benign	0.23

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: rs17727982; hg19: chr18-47435550;