rs2457965

Variant names:

• chr18-50116818-C-A
• rs2457965
• NM_001080467.3:c.28-61440G>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.28-61440G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.306 in 147,752 control chromosomes in the GnomAD database, including 7,333 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 0.31 (7333 hom., cov: 25)
• Consequence: MYO5B NM_001080467.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.436
• Publications: 4 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.444 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO5B	NM_001080467.3	c.28-61440G>T		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.28-61440G>T		intron_variant	Intron 1 of 39	1	NM_001080467.3	ENSP00000285039.6
MYO5B	ENST00000697221.1	n.399-61440G>T		intron_variant	Intron 1 of 4

Frequencies

GnomAD3 genomes AF: 0.306 AC: 45123 AN: 147654 Hom.: 7329 Cov.: 25

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.389

Gnomad AMR AF: 0.453

Gnomad ASJ AF: 0.310

Gnomad EAS AF: 0.293

Gnomad SAS AF: 0.359

Gnomad FIN AF: 0.414

Gnomad MID AF: 0.359

Gnomad NFE AF: 0.306

Gnomad OTH AF: 0.332

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

GnomAD4 genome AF: 0.306 AC: 45144 AN: 147752 Hom.: 7333 Cov.: 25 AF XY: 0.313 AC XY: 22521 AN XY: 71880

African (AFR) AF: 0.215 AC: 8553 AN: 39756

American (AMR) AF: 0.454 AC: 6771 AN: 14930

Ashkenazi Jewish (ASJ) AF: 0.310 AC: 1069 AN: 3450

East Asian (EAS) AF: 0.292 AC: 1453 AN: 4972

South Asian (SAS) AF: 0.359 AC: 1639 AN: 4562

European-Finnish (FIN) AF: 0.414 AC: 3985 AN: 9614

Middle Eastern (MID) AF: 0.355 AC: 103 AN: 290

European-Non Finnish (NFE) AF: 0.306 AC: 20541 AN: 67224

Other (OTH) AF: 0.331 AC: 677 AN: 2046

Alfa AF: 0.304 Hom.: 19772

Bravo AF: 0.305

Asia WGS AF: 0.312 AC: 1084 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.59
DANN	Benign	0.60
PhyloP100		-0.44
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: rs2457965; hg19: chr18-47643188;