chr18-49849562-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -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

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO5B	NM_001080467.3	c.4315+5G>A		splice_region_variant, intron_variant	Intron 32 of 39	ENST00000285039.12	NP_001073936.1
SNHG22	NR_117096.1	n.193-75C>T		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO5B	ENST00000285039.12	c.4315+5G>A		splice_region_variant, intron_variant	Intron 32 of 39	1	NM_001080467.3	ENSP00000285039.6

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.06e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.14
DANN	Benign	0.42

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

Publications

LitVar

Other links and lift over

dbSNP: rs488890; hg19: chr18-47375932;