18-49850107-C-A

Position:

• chr18-49850107-C-A

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
MYO5B	NM_001080467.3	c.4222-447G>T		intron_variant		ENST00000285039.12	NP_001073936.1
SNHG22	NR_117096.1	n.663C>A		non_coding_transcript_exon_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYO5B	ENST00000285039.12	c.4222-447G>T		intron_variant		1	NM_001080467.3	ENSP00000285039	P1
SNHG22	ENST00000589499.1	n.663C>A		non_coding_transcript_exon_variant	4/4	2

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

Gnomad4 AFR exome AF: 0.439

Gnomad4 AMR exome AF: 0.303

Gnomad4 ASJ exome AF: 0.531

Gnomad4 EAS exome AF: 0.106

Gnomad4 SAS exome AF: 0.290

Gnomad4 FIN exome AF: 0.380

Gnomad4 NFE exome AF: 0.484

Gnomad4 OTH exome AF: 0.436

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

Gnomad4 AFR AF: 0.437

Gnomad4 AMR AF: 0.368

Gnomad4 ASJ AF: 0.554

Gnomad4 EAS AF: 0.115

Gnomad4 SAS AF: 0.288

Gnomad4 FIN AF: 0.397

Gnomad4 NFE AF: 0.491

Gnomad4 OTH AF: 0.470

Alfa AF: 0.449 Hom.: 2650

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

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: rs669350; hg19: chr18-47376477;