rs2969931

Variant names:

• chr18-49887066-C-A
• rs2969931
• NM_001080467.3:c.3046-6611G>T

Your query was ambiguous. Multiple possible variants found:

• chr18-49887066-C-A
• chr18-49887066-C-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.3046-6611G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.577 in 151,910 control chromosomes in the GnomAD database, including 25,483 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 (25483 hom., cov: 31)
• Consequence: MYO5B NM_001080467.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.305
• 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, 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=-0.54).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.619 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO5B	NM_001080467.3	c.3046-6611G>T		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.3046-6611G>T		intron_variant	Intron 22 of 39	1	NM_001080467.3	ENSP00000285039.6
MYO5B	ENST00000697219.1	c.2842-6611G>T		intron_variant	Intron 20 of 37			ENSP00000513188.1
MYO5B	ENST00000324581.10	c.475-6611G>T		intron_variant	Intron 2 of 18	2		ENSP00000315531.7

Frequencies

GnomAD3 genomes AF: 0.577 AC: 87593 AN: 151792 Hom.: 25478 Cov.: 31

Gnomad AFR AF: 0.497

Gnomad AMI AF: 0.737

Gnomad AMR AF: 0.629

Gnomad ASJ AF: 0.650

Gnomad EAS AF: 0.535

Gnomad SAS AF: 0.562

Gnomad FIN AF: 0.545

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.616

Gnomad OTH AF: 0.619

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

GnomAD4 genome AF: 0.577 AC: 87632 AN: 151910 Hom.: 25483 Cov.: 31 AF XY: 0.576 AC XY: 42789 AN XY: 74240

African (AFR) AF: 0.496 AC: 20552 AN: 41400

American (AMR) AF: 0.629 AC: 9616 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.650 AC: 2258 AN: 3472

East Asian (EAS) AF: 0.535 AC: 2754 AN: 5150

South Asian (SAS) AF: 0.561 AC: 2697 AN: 4806

European-Finnish (FIN) AF: 0.545 AC: 5755 AN: 10550

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

European-Non Finnish (NFE) AF: 0.616 AC: 41834 AN: 67942

Other (OTH) AF: 0.617 AC: 1299 AN: 2106

Alfa AF: 0.591 Hom.: 4616

Bravo AF: 0.582

Asia WGS AF: 0.558 AC: 1941 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	8.4
DANN	Benign	0.91
PhyloP100		0.30
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: rs2969931; hg19: chr18-47413436;