18-49890700-A-G

Position:

• chr18-49890700-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.3045+4241T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.581 in 151,942 control chromosomes in the GnomAD database, including 25,810 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 0.58 (25810 hom., cov: 32)
• Consequence: MYO5B NM_001080467.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.414

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.622 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO5B	NM_001080467.3	c.3045+4241T>C		intron_variant		ENST00000285039.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO5B	ENST00000285039.12	c.3045+4241T>C		intron_variant		1	NM_001080467.3	P1
MYO5B	ENST00000324581.10	c.474+4241T>C		intron_variant		2
MYO5B	ENST00000697219.1	c.2842+4241T>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.581 AC: 88259 AN: 151824 Hom.: 25802 Cov.: 32

Gnomad AFR AF: 0.511

Gnomad AMI AF: 0.739

Gnomad AMR AF: 0.632

Gnomad ASJ AF: 0.651

Gnomad EAS AF: 0.536

Gnomad SAS AF: 0.565

Gnomad FIN AF: 0.545

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.616

Gnomad OTH AF: 0.622

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

GnomAD4 genome AF: 0.581 AC: 88307 AN: 151942 Hom.: 25810 Cov.: 32 AF XY: 0.581 AC XY: 43090 AN XY: 74216

Gnomad4 AFR AF: 0.511

Gnomad4 AMR AF: 0.632

Gnomad4 ASJ AF: 0.651

Gnomad4 EAS AF: 0.535

Gnomad4 SAS AF: 0.564

Gnomad4 FIN AF: 0.545

Gnomad4 NFE AF: 0.616

Gnomad4 OTH AF: 0.619

Alfa AF: 0.597 Hom.: 4561

Bravo AF: 0.587

Asia WGS AF: 0.563 AC: 1958 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.9
DANN	Benign	0.36

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: rs17800754; hg19: chr18-47417070;