rs633667

Variant names:

• chr18-49845523-T-C
• rs633667
• NM_001080467.3:c.4459+1623A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001080467.3(MYO5B):​c.4459+1623A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.425 in 152,102 control chromosomes in the GnomAD database, including 14,407 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 0.43 (14407 hom., cov: 33)
• Consequence: MYO5B NM_001080467.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.962
• Publications: 3 publications found

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]

SNHG22 (HGNC:50285): (small nucleolar RNA host gene 22)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.487 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO5B	NM_001080467.3	c.4459+1623A>G		intron_variant	Intron 33 of 39	ENST00000285039.12	NP_001073936.1
SNHG22	NR_117096.1	n.193-4114T>C		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO5B	ENST00000285039.12	c.4459+1623A>G		intron_variant	Intron 33 of 39	1	NM_001080467.3	ENSP00000285039.6

Frequencies

GnomAD3 genomes AF: 0.426 AC: 64696 AN: 151984 Hom.: 14414 Cov.: 33

Gnomad AFR AF: 0.381

Gnomad AMI AF: 0.664

Gnomad AMR AF: 0.366

Gnomad ASJ AF: 0.554

Gnomad EAS AF: 0.111

Gnomad SAS AF: 0.312

Gnomad FIN AF: 0.396

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.492

Gnomad OTH AF: 0.470

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

GnomAD4 genome AF: 0.425 AC: 64697 AN: 152102 Hom.: 14407 Cov.: 33 AF XY: 0.418 AC XY: 31107 AN XY: 74364

African (AFR) AF: 0.380 AC: 15763 AN: 41470

American (AMR) AF: 0.365 AC: 5586 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.554 AC: 1920 AN: 3468

East Asian (EAS) AF: 0.111 AC: 572 AN: 5168

South Asian (SAS) AF: 0.311 AC: 1503 AN: 4826

European-Finnish (FIN) AF: 0.396 AC: 4190 AN: 10574

Middle Eastern (MID) AF: 0.548 AC: 161 AN: 294

European-Non Finnish (NFE) AF: 0.492 AC: 33413 AN: 67980

Other (OTH) AF: 0.466 AC: 986 AN: 2114

Alfa AF: 0.441 Hom.: 2568

Bravo AF: 0.421

Asia WGS AF: 0.254 AC: 885 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.4
DANN	Benign	0.75
PhyloP100		-0.96
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs633667; hg19: chr18-47371893;