rs578211

Variant names:

• chr18-49868025-A-C
• rs578211
• NM_001080467.3:c.3604-3645T>G

Your query was ambiguous. Multiple possible variants found:

• chr18-49868025-A-C
• chr18-49868025-A-G
• chr18-49868025-A-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.3604-3645T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.737 in 151,970 control chromosomes in the GnomAD database, including 41,400 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 0.74 (41400 hom., cov: 32)
• Consequence: MYO5B NM_001080467.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.293
• Publications: 7 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.825 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO5B	NM_001080467.3	c.3604-3645T>G		intron_variant	Intron 27 of 39	ENST00000285039.12	NP_001073936.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO5B	ENST00000285039.12	c.3604-3645T>G		intron_variant	Intron 27 of 39	1	NM_001080467.3	ENSP00000285039.6

Frequencies

GnomAD3 genomes AF: 0.737 AC: 111854 AN: 151852 Hom.: 41373 Cov.: 32

Gnomad AFR AF: 0.694

Gnomad AMI AF: 0.852

Gnomad AMR AF: 0.837

Gnomad ASJ AF: 0.814

Gnomad EAS AF: 0.821

Gnomad SAS AF: 0.748

Gnomad FIN AF: 0.685

Gnomad MID AF: 0.818

Gnomad NFE AF: 0.734

Gnomad OTH AF: 0.778

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

GnomAD4 genome AF: 0.737 AC: 111932 AN: 151970 Hom.: 41400 Cov.: 32 AF XY: 0.739 AC XY: 54916 AN XY: 74294

African (AFR) AF: 0.693 AC: 28722 AN: 41420

American (AMR) AF: 0.837 AC: 12789 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.814 AC: 2826 AN: 3470

East Asian (EAS) AF: 0.820 AC: 4249 AN: 5180

South Asian (SAS) AF: 0.749 AC: 3609 AN: 4818

European-Finnish (FIN) AF: 0.685 AC: 7209 AN: 10530

Middle Eastern (MID) AF: 0.829 AC: 242 AN: 292

European-Non Finnish (NFE) AF: 0.734 AC: 49868 AN: 67968

Other (OTH) AF: 0.778 AC: 1641 AN: 2108

Alfa AF: 0.745 Hom.: 22298

Bravo AF: 0.749

Asia WGS AF: 0.798 AC: 2754 AN: 3454

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.8
DANN	Benign	0.85
PhyloP100		-0.29
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: rs578211; hg19: chr18-47394395;