18-49851183-G-T

Variant names:

• chr18-49851183-G-T
• rs546341
• NM_001080467.3:c.4222-1523C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001080467.3(MYO5B):​c.4222-1523C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.848 in 152,186 control chromosomes in the GnomAD database, including 54,836 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 0.85 (54834 hom., cov: 32)
  • Exomes 𝑓: 1.0 (2 hom.)
• Consequence: MYO5B NM_001080467.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.27
• Publications: 3 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.935 is higher than 0.05.

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.4222-1523C>A		intron	N/A	NP_001073936.1	Q9ULV0-1
	SNHG22	NR_117096.1		n.*124G>T		downstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO5B	ENST00000285039.12	TSL:1 MANE Select	c.4222-1523C>A		intron	N/A	ENSP00000285039.6	Q9ULV0-1
	MYO5B	ENST00000697219.1		c.3955-1523C>A		intron	N/A	ENSP00000513188.1	A0A8V8TM52
	MYO5B	ENST00000908785.1		c.3603+20984C>A		intron	N/A	ENSP00000578844.1

Frequencies

GnomAD3 genomes AF: 0.848 AC: 128978 AN: 152064 Hom.: 54782 Cov.: 32

Gnomad AFR AF: 0.872

Gnomad AMI AF: 0.932

Gnomad AMR AF: 0.892

Gnomad ASJ AF: 0.866

Gnomad EAS AF: 0.957

Gnomad SAS AF: 0.911

Gnomad FIN AF: 0.803

Gnomad MID AF: 0.877

Gnomad NFE AF: 0.815

Gnomad OTH AF: 0.867

GnomAD4 exome AF: 1.00 AC: 4 AN: 4 Hom.: 2 AF XY: 1.00 AC XY: 4 AN XY: 4

African (AFR) AC: 0 AN: 0

American (AMR) AF: 1.00 AC: 2 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 1.00 AC: 2 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.848 AC: 129089 AN: 152182 Hom.: 54834 Cov.: 32 AF XY: 0.852 AC XY: 63409 AN XY: 74386

African (AFR) AF: 0.872 AC: 36212 AN: 41506

American (AMR) AF: 0.892 AC: 13653 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.866 AC: 3006 AN: 3472

East Asian (EAS) AF: 0.957 AC: 4944 AN: 5166

South Asian (SAS) AF: 0.912 AC: 4390 AN: 4816

European-Finnish (FIN) AF: 0.803 AC: 8500 AN: 10588

Middle Eastern (MID) AF: 0.884 AC: 260 AN: 294

European-Non Finnish (NFE) AF: 0.815 AC: 55443 AN: 68016

Other (OTH) AF: 0.866 AC: 1831 AN: 2114

Alfa AF: 0.825 Hom.: 23041

Bravo AF: 0.856

Asia WGS AF: 0.935 AC: 3252 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.24
DANN	Benign	0.83
PhyloP100		-2.3
Mutation Taster		=100/0	polymorphism (auto)

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: rs546341; hg19: chr18-47377553;