18-49935958-T-C

Variant names:

• chr18-49935958-T-C
• rs4939921
• NM_001080467.3:c.2003+294A>G

Variant summary

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

The NM_001080467.3(MYO5B):​c.2003+294A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.098 in 152,306 control chromosomes in the GnomAD database, including 981 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 0.098 (981 hom., cov: 33)
• Consequence: MYO5B NM_001080467.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.391
• 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]

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.294 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.2003+294A>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.2003+294A>G		intron	N/A	ENSP00000285039.6	Q9ULV0-1
	MYO5B	ENST00000697219.1		c.1799+294A>G		intron	N/A	ENSP00000513188.1	A0A8V8TM52
	MYO5B	ENST00000908785.1		c.2003+294A>G		intron	N/A	ENSP00000578844.1

Frequencies

GnomAD3 genomes AF: 0.0980 AC: 14914 AN: 152188 Hom.: 980 Cov.: 33

Gnomad AFR AF: 0.0382

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.0848

Gnomad EAS AF: 0.307

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0997

Gnomad OTH AF: 0.0958

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

GnomAD4 genome AF: 0.0980 AC: 14926 AN: 152306 Hom.: 981 Cov.: 33 AF XY: 0.103 AC XY: 7689 AN XY: 74464

African (AFR) AF: 0.0381 AC: 1585 AN: 41588

American (AMR) AF: 0.128 AC: 1966 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0848 AC: 294 AN: 3468

East Asian (EAS) AF: 0.307 AC: 1587 AN: 5176

South Asian (SAS) AF: 0.172 AC: 828 AN: 4824

European-Finnish (FIN) AF: 0.146 AC: 1554 AN: 10612

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0997 AC: 6780 AN: 68022

Other (OTH) AF: 0.0991 AC: 209 AN: 2110

Alfa AF: 0.0955 Hom.: 1759

Bravo AF: 0.0925

Asia WGS AF: 0.218 AC: 754 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.32
DANN	Benign	0.46
PhyloP100		-0.39
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: rs4939921; hg19: chr18-47462328;