18-49849733-C-T

Variant names:

• chr18-49849733-C-T
• rs490648
• ENST00000592688.1:c.-142G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000592688.1(MYO5B):​c.-142G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000929 in 1,076,060 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000093 (0 hom.)
• Consequence: MYO5B ENST00000592688.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.271
• Publications: 10 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000592688.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO5B	NM_001080467.3	MANE Select	c.4222-73G>A		intron	N/A	NP_001073936.1	Q9ULV0-1
	SNHG22	NR_117096.1		n.289C>T		non_coding_transcript_exon	Exon 4 of 4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO5B	ENST00000592688.1	TSL:1	c.-142G>A		5_prime_UTR	Exon 1 of 9	ENSP00000466368.1	Q9ULV0-3
	MYO5B	ENST00000285039.12	TSL:1 MANE Select	c.4222-73G>A		intron	N/A	ENSP00000285039.6	Q9ULV0-1
	MYO5B	ENST00000697219.1		c.3955-73G>A		intron	N/A	ENSP00000513188.1	A0A8V8TM52

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000929 AC: 10 AN: 1076060 Hom.: 0 Cov.: 14 AF XY: 0.00000902 AC XY: 5 AN XY: 554030

African (AFR) AF: 0.00 AC: 0 AN: 26046

American (AMR) AF: 0.00 AC: 0 AN: 44194

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23718

East Asian (EAS) AF: 0.00 AC: 0 AN: 38016

South Asian (SAS) AF: 0.00 AC: 0 AN: 78642

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44294

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4852

European-Non Finnish (NFE) AF: 0.0000130 AC: 10 AN: 768518

Other (OTH) AF: 0.00 AC: 0 AN: 47780

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 776

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.4
DANN	Benign	0.93
PhyloP100		-0.27
PromoterAI		-0.023	Neutral

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: rs490648; hg19: chr18-47376103;