rs490648

Positions:

• chr18-49849733-C-G
• chr18-49849733-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000592688.1(MYO5B):​c.-142G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.443 in 1,224,514 control chromosomes in the GnomAD database, including 125,690 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.44 (15377 hom., cov: 33)
  • Exomes 𝑓: 0.44 (110313 hom.)
• Consequence: MYO5B ENST00000592688.1 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.271

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:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 18-49849733-C-G is Benign according to our data. Variant chr18-49849733-C-G is described in ClinVar as [Benign]. Clinvar id is 1246653.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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.4222-73G>C		intron_variant		ENST00000285039.12	NP_001073936.1
SNHG22	NR_117096.1	n.289C>G		non_coding_transcript_exon_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYO5B	ENST00000285039.12	c.4222-73G>C		intron_variant		1	NM_001080467.3	ENSP00000285039.6

Frequencies

GnomAD3 genomes AF: 0.441 AC: 67076 AN: 151974 Hom.: 15380 Cov.: 33

Gnomad AFR AF: 0.435

Gnomad AMI AF: 0.665

Gnomad AMR AF: 0.372

Gnomad ASJ AF: 0.553

Gnomad EAS AF: 0.117

Gnomad SAS AF: 0.314

Gnomad FIN AF: 0.396

Gnomad MID AF: 0.545

Gnomad NFE AF: 0.491

Gnomad OTH AF: 0.478

GnomAD4 exome AF: 0.444 AC: 475947 AN: 1072422 Hom.: 110313 Cov.: 14 AF XY: 0.443 AC XY: 244775 AN XY: 552234

Gnomad4 AFR exome AF: 0.435

Gnomad4 AMR exome AF: 0.269

Gnomad4 ASJ exome AF: 0.553

Gnomad4 EAS exome AF: 0.122

Gnomad4 SAS exome AF: 0.330

Gnomad4 FIN exome AF: 0.384

Gnomad4 NFE exome AF: 0.482

Gnomad4 OTH exome AF: 0.438

GnomAD4 genome AF: 0.441 AC: 67086 AN: 152092 Hom.: 15377 Cov.: 33 AF XY: 0.433 AC XY: 32228 AN XY: 74354

Gnomad4 AFR AF: 0.434

Gnomad4 AMR AF: 0.372

Gnomad4 ASJ AF: 0.553

Gnomad4 EAS AF: 0.116

Gnomad4 SAS AF: 0.313

Gnomad4 FIN AF: 0.396

Gnomad4 NFE AF: 0.491

Gnomad4 OTH AF: 0.474

Alfa AF: 0.315 Hom.: 776

Bravo AF: 0.439

Asia WGS AF: 0.260 AC: 907 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.8
DANN	Benign	0.33

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: rs490648; hg19: chr18-47376103; COSMIC: COSV53217494;