18-49935958-T-C

Variant names:

• chr18-49935958-T-C
• rs4939921
• NM_001080467.3:c.2003+294A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001080467.3(MYO5B):​c.2003+294A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.098 in 152,306 control chromosomes in the GnomAD database, including 981 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 0.098 (981 hom., cov: 33)
• Consequence: MYO5B NM_001080467.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.391

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.294 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO5B	NM_001080467.3	c.2003+294A>G		intron_variant	Intron 16 of 39	ENST00000285039.12	NP_001073936.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO5B	ENST00000285039.12	c.2003+294A>G		intron_variant	Intron 16 of 39	1	NM_001080467.3	ENSP00000285039.6
MYO5B	ENST00000697219.1	c.1799+294A>G		intron_variant	Intron 14 of 37			ENSP00000513188.1

Frequencies

GnomAD3 genomes AF: 0.0980 AC: 14914 AN: 152188 Hom.: 980 Cov.: 33

Gnomad AFR AF: 0.0382

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.0848

Gnomad EAS AF: 0.307

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0997

Gnomad OTH AF: 0.0958

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

GnomAD4 genome AF: 0.0980 AC: 14926 AN: 152306 Hom.: 981 Cov.: 33 AF XY: 0.103 AC XY: 7689 AN XY: 74464

Gnomad4 AFR AF: 0.0381

Gnomad4 AMR AF: 0.128

Gnomad4 ASJ AF: 0.0848

Gnomad4 EAS AF: 0.307

Gnomad4 SAS AF: 0.172

Gnomad4 FIN AF: 0.146

Gnomad4 NFE AF: 0.0997

Gnomad4 OTH AF: 0.0991

Alfa AF: 0.0976 Hom.: 1135

Bravo AF: 0.0925

Asia WGS AF: 0.218 AC: 754 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	0.32
DANN	Benign	0.46

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

Publications

LitVar

Other links and lift over

dbSNP: rs4939921; hg19: chr18-47462328;