18-49886819-C-T

Position:

• chr18-49886819-C-T

Variant summary

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

The NM_001080467.3(MYO5B):​c.3046-6364G>A 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 151,766 control chromosomes in the GnomAD database, including 25,778 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 (25778 hom., cov: 30)
• Consequence: MYO5B NM_001080467.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.180

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 = 0.621 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO5B	NM_001080467.3	c.3046-6364G>A		intron_variant		ENST00000285039.12	NP_001073936.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYO5B	ENST00000285039.12	c.3046-6364G>A		intron_variant		1	NM_001080467.3	ENSP00000285039.6
MYO5B	ENST00000697219.1	c.2842-6364G>A		intron_variant				ENSP00000513188.1
MYO5B	ENST00000324581.10	c.475-6364G>A		intron_variant		2		ENSP00000315531.7

Frequencies

GnomAD3 genomes AF: 0.581 AC: 88143 AN: 151648 Hom.: 25770 Cov.: 30

Gnomad AFR AF: 0.511

Gnomad AMI AF: 0.737

Gnomad AMR AF: 0.631

Gnomad ASJ AF: 0.651

Gnomad EAS AF: 0.537

Gnomad SAS AF: 0.563

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: 88191 AN: 151766 Hom.: 25778 Cov.: 30 AF XY: 0.581 AC XY: 43033 AN XY: 74120

Gnomad4 AFR AF: 0.511

Gnomad4 AMR AF: 0.632

Gnomad4 ASJ AF: 0.651

Gnomad4 EAS AF: 0.536

Gnomad4 SAS AF: 0.562

Gnomad4 FIN AF: 0.545

Gnomad4 NFE AF: 0.616

Gnomad4 OTH AF: 0.620

Alfa AF: 0.596 Hom.: 4560

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	-0.90
CADD	Benign	5.2
DANN	Benign	0.81

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: rs1787606; hg19: chr18-47413189;