rs1623892

Positions:

• chr18-49930071-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.2004-473T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.486 in 152,058 control chromosomes in the GnomAD database, including 18,671 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 0.49 (18671 hom., cov: 32)
• Consequence: MYO5B NM_001080467.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.210

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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.556 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO5B	NM_001080467.3	c.2004-473T>C		intron_variant		ENST00000285039.12	NP_001073936.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYO5B	ENST00000285039.12	c.2004-473T>C		intron_variant		1	NM_001080467.3	ENSP00000285039.6
MYO5B	ENST00000697219.1	c.1800-473T>C		intron_variant				ENSP00000513188.1

Frequencies

GnomAD3 genomes AF: 0.486 AC: 73807 AN: 151940 Hom.: 18669 Cov.: 32

Gnomad AFR AF: 0.423

Gnomad AMI AF: 0.728

Gnomad AMR AF: 0.386

Gnomad ASJ AF: 0.587

Gnomad EAS AF: 0.224

Gnomad SAS AF: 0.462

Gnomad FIN AF: 0.472

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.561

Gnomad OTH AF: 0.506

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

GnomAD4 genome AF: 0.486 AC: 73830 AN: 152058 Hom.: 18671 Cov.: 32 AF XY: 0.480 AC XY: 35668 AN XY: 74336

Gnomad4 AFR AF: 0.423

Gnomad4 AMR AF: 0.385

Gnomad4 ASJ AF: 0.587

Gnomad4 EAS AF: 0.224

Gnomad4 SAS AF: 0.460

Gnomad4 FIN AF: 0.472

Gnomad4 NFE AF: 0.561

Gnomad4 OTH AF: 0.502

Alfa AF: 0.529 Hom.: 10936

Bravo AF: 0.472

Asia WGS AF: 0.371 AC: 1292 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.72
DANN	Benign	0.70

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: rs1623892; hg19: chr18-47456441;