18-49849562-C-T

Variant names:

• chr18-49849562-C-T
• rs488890
• NM_001080467.3:c.4315+5G>A

Variant summary

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

The NM_001080467.3(MYO5B):​c.4315+5G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,451,358 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: MYO5B NM_001080467.3 splice_region, intron
• Scores: Splicing: ADA: 0.1858
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.32
• Publications: 15 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=-0.9).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080467.3. 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.4315+5G>A		splice_region intron	N/A	NP_001073936.1	Q9ULV0-1
	SNHG22	NR_117096.1		n.193-75C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO5B	ENST00000285039.12	TSL:1 MANE Select	c.4315+5G>A		splice_region intron	N/A	ENSP00000285039.6	Q9ULV0-1
	MYO5B	ENST00000592688.1	TSL:1	c.25+5G>A		splice_region intron	N/A	ENSP00000466368.1	Q9ULV0-3
	MYO5B	ENST00000697219.1		c.4048+5G>A		splice_region intron	N/A	ENSP00000513188.1	A0A8V8TM52

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1451358 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 722688

African (AFR) AF: 0.00 AC: 0 AN: 33254

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26078

East Asian (EAS) AF: 0.00 AC: 0 AN: 39674

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86032

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4384

European-Non Finnish (NFE) AF: 9.06e-7 AC: 1 AN: 1103886

Other (OTH) AF: 0.00 AC: 0 AN: 59932

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.14
DANN	Benign	0.42
PhyloP100		-4.3
PromoterAI		-0.16	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.19
dbscSNV1_RF	Benign	0.15
SpliceAI score (max)		0.090		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: rs488890; hg19: chr18-47375932;