rs578211

Positions:

• chr18-49868025-A-C
• chr18-49868025-A-G
• chr18-49868025-A-T

Variant summary

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

The NM_001080467.3(MYO5B):​c.3604-3645T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.737 in 151,970 control chromosomes in the GnomAD database, including 41,400 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 0.74 (41400 hom., cov: 32)
• Consequence: MYO5B NM_001080467.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.293

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.825 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO5B	NM_001080467.3	c.3604-3645T>G		intron_variant		ENST00000285039.12	NP_001073936.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYO5B	ENST00000285039.12	c.3604-3645T>G		intron_variant		1	NM_001080467.3	ENSP00000285039	P1

Frequencies

GnomAD3 genomes AF: 0.737 AC: 111854 AN: 151852 Hom.: 41373 Cov.: 32

Gnomad AFR AF: 0.694

Gnomad AMI AF: 0.852

Gnomad AMR AF: 0.837

Gnomad ASJ AF: 0.814

Gnomad EAS AF: 0.821

Gnomad SAS AF: 0.748

Gnomad FIN AF: 0.685

Gnomad MID AF: 0.818

Gnomad NFE AF: 0.734

Gnomad OTH AF: 0.778

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

GnomAD4 genome AF: 0.737 AC: 111932 AN: 151970 Hom.: 41400 Cov.: 32 AF XY: 0.739 AC XY: 54916 AN XY: 74294

Gnomad4 AFR AF: 0.693

Gnomad4 AMR AF: 0.837

Gnomad4 ASJ AF: 0.814

Gnomad4 EAS AF: 0.820

Gnomad4 SAS AF: 0.749

Gnomad4 FIN AF: 0.685

Gnomad4 NFE AF: 0.734

Gnomad4 OTH AF: 0.778

Alfa AF: 0.746 Hom.: 19940

Bravo AF: 0.749

Asia WGS AF: 0.798 AC: 2754 AN: 3454

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.8
DANN	Benign	0.85

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: rs578211; hg19: chr18-47394395;