18-49885800-A-T

Variant names:

• chr18-49885800-A-T
• rs10502903
• NM_001080467.3:c.3046-5345T>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.3046-5345T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.581 in 151,914 control chromosomes in the GnomAD database, including 25,797 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 0.58 (25797 hom., cov: 30)
• Consequence: MYO5B NM_001080467.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.596
• Publications: 5 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, PanelApp Australia, 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 (AMR) allele frequency at 95% confidence interval = 0.621 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO5B	NM_001080467.3	c.3046-5345T>A		intron_variant	Intron 22 of 39	ENST00000285039.12	NP_001073936.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO5B	ENST00000285039.12	c.3046-5345T>A		intron_variant	Intron 22 of 39	1	NM_001080467.3	ENSP00000285039.6
MYO5B	ENST00000697219.1	c.2842-5345T>A		intron_variant	Intron 20 of 37			ENSP00000513188.1
MYO5B	ENST00000324581.10	c.475-5345T>A		intron_variant	Intron 2 of 18	2		ENSP00000315531.7

Frequencies

GnomAD3 genomes AF: 0.581 AC: 88211 AN: 151794 Hom.: 25789 Cov.: 30

Gnomad AFR AF: 0.511

Gnomad AMI AF: 0.738

Gnomad AMR AF: 0.632

Gnomad ASJ AF: 0.651

Gnomad EAS AF: 0.536

Gnomad SAS AF: 0.563

Gnomad FIN AF: 0.546

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.615

Gnomad OTH AF: 0.621

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

GnomAD4 genome AF: 0.581 AC: 88259 AN: 151914 Hom.: 25797 Cov.: 30 AF XY: 0.581 AC XY: 43108 AN XY: 74254

African (AFR) AF: 0.511 AC: 21142 AN: 41402

American (AMR) AF: 0.632 AC: 9659 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.651 AC: 2254 AN: 3464

East Asian (EAS) AF: 0.535 AC: 2753 AN: 5144

South Asian (SAS) AF: 0.563 AC: 2707 AN: 4812

European-Finnish (FIN) AF: 0.546 AC: 5751 AN: 10528

Middle Eastern (MID) AF: 0.667 AC: 196 AN: 294

European-Non Finnish (NFE) AF: 0.615 AC: 41820 AN: 67960

Other (OTH) AF: 0.618 AC: 1305 AN: 2110

Alfa AF: 0.593 Hom.: 3295

Bravo AF: 0.587

Asia WGS AF: 0.563 AC: 1959 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.43
DANN	Benign	0.58
PhyloP100		-0.60
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: rs10502903; hg19: chr18-47412170;