rs669350

Variant names:

• chr18-49850107-C-A
• rs669350
• NM_001080467.3:c.4222-447G>T

Your query was ambiguous. Multiple possible variants found:

• chr18-49850107-C-A
• chr18-49850107-C-T

Variant summary

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

The NM_001080467.3(MYO5B):​c.4222-447G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.431 in 277,146 control chromosomes in the GnomAD database, including 27,357 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 0.44 (15326 hom., cov: 33)
  • Exomes 𝑓: 0.42 (12031 hom.)
• Consequence: MYO5B NM_001080467.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.669
• Publications: 4 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=-0.82).
• 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.4222-447G>T		intron_variant	Intron 31 of 39	ENST00000285039.12	NP_001073936.1
SNHG22	NR_117096.1	n.663C>A		non_coding_transcript_exon_variant	Exon 4 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO5B	ENST00000285039.12	c.4222-447G>T		intron_variant	Intron 31 of 39	1	NM_001080467.3	ENSP00000285039.6

Frequencies

GnomAD3 genomes AF: 0.441 AC: 66940 AN: 151926 Hom.: 15328 Cov.: 33

Gnomad AFR AF: 0.437

Gnomad AMI AF: 0.667

Gnomad AMR AF: 0.369

Gnomad ASJ AF: 0.554

Gnomad EAS AF: 0.116

Gnomad SAS AF: 0.288

Gnomad FIN AF: 0.397

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.491

Gnomad OTH AF: 0.474

GnomAD4 exome AF: 0.419 AC: 52372 AN: 125102 Hom.: 12031 Cov.: 0 AF XY: 0.406 AC XY: 26825 AN XY: 66090

African (AFR) AF: 0.439 AC: 1711 AN: 3898

American (AMR) AF: 0.303 AC: 1725 AN: 5692

Ashkenazi Jewish (ASJ) AF: 0.531 AC: 1526 AN: 2874

East Asian (EAS) AF: 0.106 AC: 631 AN: 5928

South Asian (SAS) AF: 0.290 AC: 5869 AN: 20216

European-Finnish (FIN) AF: 0.380 AC: 2203 AN: 5794

Middle Eastern (MID) AF: 0.456 AC: 216 AN: 474

European-Non Finnish (NFE) AF: 0.484 AC: 35683 AN: 73780

Other (OTH) AF: 0.436 AC: 2808 AN: 6446

GnomAD4 genome AF: 0.440 AC: 66952 AN: 152044 Hom.: 15326 Cov.: 33 AF XY: 0.432 AC XY: 32129 AN XY: 74314

African (AFR) AF: 0.437 AC: 18098 AN: 41450

American (AMR) AF: 0.368 AC: 5632 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.554 AC: 1919 AN: 3464

East Asian (EAS) AF: 0.115 AC: 596 AN: 5182

South Asian (SAS) AF: 0.288 AC: 1384 AN: 4808

European-Finnish (FIN) AF: 0.397 AC: 4206 AN: 10598

Middle Eastern (MID) AF: 0.538 AC: 157 AN: 292

European-Non Finnish (NFE) AF: 0.491 AC: 33363 AN: 67948

Other (OTH) AF: 0.470 AC: 993 AN: 2112

Alfa AF: 0.449 Hom.: 2719

Bravo AF: 0.439

Asia WGS AF: 0.249 AC: 867 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.43
DANN	Benign	0.75
PhyloP100		-0.67
PromoterAI		-0.0072	Neutral
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: rs669350; hg19: chr18-47376477;