rs9954152

Variant names:

• chr18-50113638-A-C
• rs9954152
• NM_001080467.3:c.28-58260T>G

Your query was ambiguous. Multiple possible variants found:

• chr18-50113638-A-C
• chr18-50113638-A-T

Variant summary

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

The NM_001080467.3(MYO5B):​c.28-58260T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 152,158 control chromosomes in the GnomAD database, including 7,538 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 0.30 (7538 hom., cov: 33)
• Consequence: MYO5B NM_001080467.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.22
• Publications: 2 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]

MYO5B Gene-Disease associations (from GenCC):

• microvillus inclusion disease

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Labcorp Genetics (formerly Invitae)
• cholestasis, progressive familial intrahepatic, 10

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• progressive familial intrahepatic cholestasis type 1

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.446 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.28-58260T>G		intron	N/A	NP_001073936.1	Q9ULV0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO5B	ENST00000285039.12	TSL:1 MANE Select	c.28-58260T>G		intron	N/A	ENSP00000285039.6	Q9ULV0-1
	MYO5B	ENST00000908785.1		c.28-58260T>G		intron	N/A	ENSP00000578844.1
	MYO5B	ENST00000697221.1		n.399-58260T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.304 AC: 46194 AN: 152040 Hom.: 7531 Cov.: 33

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.411

Gnomad AMR AF: 0.454

Gnomad ASJ AF: 0.311

Gnomad EAS AF: 0.292

Gnomad SAS AF: 0.354

Gnomad FIN AF: 0.414

Gnomad MID AF: 0.363

Gnomad NFE AF: 0.307

Gnomad OTH AF: 0.332

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.304 AC: 46226 AN: 152158 Hom.: 7538 Cov.: 33 AF XY: 0.312 AC XY: 23176 AN XY: 74374

African (AFR) AF: 0.206 AC: 8565 AN: 41528

American (AMR) AF: 0.455 AC: 6954 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.311 AC: 1079 AN: 3472

East Asian (EAS) AF: 0.291 AC: 1509 AN: 5180

South Asian (SAS) AF: 0.355 AC: 1712 AN: 4818

European-Finnish (FIN) AF: 0.414 AC: 4376 AN: 10560

Middle Eastern (MID) AF: 0.366 AC: 107 AN: 292

European-Non Finnish (NFE) AF: 0.307 AC: 20849 AN: 67988

Other (OTH) AF: 0.331 AC: 700 AN: 2114

Alfa AF: 0.285 Hom.: 3349

Bravo AF: 0.304

Asia WGS AF: 0.316 AC: 1098 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.6
DANN	Benign	0.65
PhyloP100		1.2
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: rs9954152; hg19: chr18-47640008;