rs7244679

Variant names:

• chr18-49939588-G-A
• rs7244679
• NM_001080467.3:c.1753-2191C>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.1753-2191C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 152,022 control chromosomes in the GnomAD database, including 3,667 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 0.20 (3667 hom., cov: 32)
• Consequence: MYO5B NM_001080467.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.949
• Publications: 0 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 (AFR) allele frequency at 95% confidence interval = 0.348 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO5B	NM_001080467.3	c.1753-2191C>T		intron_variant	Intron 14 of 39	ENST00000285039.12	NP_001073936.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO5B	ENST00000285039.12	c.1753-2191C>T		intron_variant	Intron 14 of 39	1	NM_001080467.3	ENSP00000285039.6
MYO5B	ENST00000697219.1	c.1549-2191C>T		intron_variant	Intron 12 of 37			ENSP00000513188.1

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29710 AN: 151904 Hom.: 3663 Cov.: 32

Gnomad AFR AF: 0.353

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.0606

Gnomad SAS AF: 0.0958

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.165

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

GnomAD4 genome AF: 0.196 AC: 29738 AN: 152022 Hom.: 3667 Cov.: 32 AF XY: 0.190 AC XY: 14147 AN XY: 74312

African (AFR) AF: 0.353 AC: 14620 AN: 41434

American (AMR) AF: 0.129 AC: 1974 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.115 AC: 400 AN: 3470

East Asian (EAS) AF: 0.0603 AC: 312 AN: 5172

South Asian (SAS) AF: 0.0954 AC: 459 AN: 4810

European-Finnish (FIN) AF: 0.148 AC: 1559 AN: 10558

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.147 AC: 9973 AN: 67978

Other (OTH) AF: 0.166 AC: 349 AN: 2108

Alfa AF: 0.167 Hom.: 987

Bravo AF: 0.202

Asia WGS AF: 0.0940 AC: 327 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	0.44
DANN	Benign	0.26
PhyloP100		-0.95
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: rs7244679; hg19: chr18-47465958;