18-50072723-A-G

Variant names:

• chr18-50072723-A-G
• rs16951446
• NM_001080467.3:c.28-17345T>C

Variant summary

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

The NM_001080467.3(MYO5B):​c.28-17345T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.093 in 152,252 control chromosomes in the GnomAD database, including 1,215 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 0.093 (1215 hom., cov: 32)
• Consequence: MYO5B NM_001080467.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.199
• Publications: 1 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.224 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO5B	NM_001080467.3	c.28-17345T>C		intron_variant	Intron 1 of 39	ENST00000285039.12	NP_001073936.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO5B	ENST00000285039.12	c.28-17345T>C		intron_variant	Intron 1 of 39	1	NM_001080467.3	ENSP00000285039.6
MYO5B	ENST00000586036.1	n.378-17345T>C		intron_variant	Intron 1 of 2	4
MYO5B	ENST00000697221.1	n.399-17345T>C		intron_variant	Intron 1 of 4

Frequencies

GnomAD3 genomes AF: 0.0930 AC: 14145 AN: 152134 Hom.: 1211 Cov.: 32

Gnomad AFR AF: 0.228

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.0513

Gnomad ASJ AF: 0.0666

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0139

Gnomad FIN AF: 0.0232

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0465

Gnomad OTH AF: 0.0817

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

GnomAD4 genome AF: 0.0930 AC: 14159 AN: 152252 Hom.: 1215 Cov.: 32 AF XY: 0.0892 AC XY: 6644 AN XY: 74450

African (AFR) AF: 0.228 AC: 9463 AN: 41506

American (AMR) AF: 0.0511 AC: 781 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0666 AC: 231 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.0139 AC: 67 AN: 4826

European-Finnish (FIN) AF: 0.0232 AC: 247 AN: 10628

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0465 AC: 3164 AN: 68014

Other (OTH) AF: 0.0808 AC: 171 AN: 2116

Alfa AF: 0.0575 Hom.: 248

Bravo AF: 0.103

Asia WGS AF: 0.0220 AC: 76 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.8
DANN	Benign	0.41
PhyloP100		0.20
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: rs16951446; hg19: chr18-47599093;