18-49929610-GAAAAAAA-GAAAAAAAAA

Variant names:

• chr18-49929610-G-GAA
• rs56278513
• NM_001080467.3:c.2004-14_2004-13dupTT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_001080467.3(MYO5B):​c.2004-14_2004-13dupTT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0094 (6 hom., cov: 0)
  • Exomes 𝑓: 0.0072 (7 hom.)
• Consequence: MYO5B NM_001080467.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.06

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 -8 ACMG points.

• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00945 (1255/132818) while in subpopulation SAS AF= 0.0192 (78/4056). AF 95% confidence interval is 0.0158. There are 6 homozygotes in gnomad4. There are 557 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO5B	NM_001080467.3	c.2004-14_2004-13dupTT		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.2004-13_2004-12insTT		intron_variant	Intron 16 of 39	1	NM_001080467.3	ENSP00000285039.6
MYO5B	ENST00000697219.1	c.1800-13_1800-12insTT		intron_variant	Intron 14 of 37			ENSP00000513188.1

Frequencies

GnomAD3 genomes AF: 0.00945 AC: 1256 AN: 132840 Hom.: 6 Cov.: 0

Gnomad AFR AF: 0.00305

Gnomad AMI AF: 0.00476

Gnomad AMR AF: 0.00480

Gnomad ASJ AF: 0.0256

Gnomad EAS AF: 0.000433

Gnomad SAS AF: 0.0194

Gnomad FIN AF: 0.00378

Gnomad MID AF: 0.0282

Gnomad NFE AF: 0.0138

Gnomad OTH AF: 0.0105

GnomAD3 exomes AF: 0.00539 AC: 617 AN: 114366 Hom.: 1 AF XY: 0.00527 AC XY: 325 AN XY: 61680

Gnomad AFR exome AF: 0.00161

Gnomad AMR exome AF: 0.00304

Gnomad ASJ exome AF: 0.0108

Gnomad EAS exome AF: 0.000116

Gnomad SAS exome AF: 0.00668

Gnomad FIN exome AF: 0.00159

Gnomad NFE exome AF: 0.00722

Gnomad OTH exome AF: 0.00491

GnomAD4 exome AF: 0.00718 AC: 8266 AN: 1151292 Hom.: 7 Cov.: 0 AF XY: 0.00725 AC XY: 4172 AN XY: 575288

Gnomad4 AFR exome AF: 0.00135

Gnomad4 AMR exome AF: 0.00259

Gnomad4 ASJ exome AF: 0.0115

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00896

Gnomad4 FIN exome AF: 0.00246

Gnomad4 NFE exome AF: 0.00778

Gnomad4 OTH exome AF: 0.00608

GnomAD4 genome AF: 0.00945 AC: 1255 AN: 132818 Hom.: 6 Cov.: 0 AF XY: 0.00878 AC XY: 557 AN XY: 63438

Gnomad4 AFR AF: 0.00305

Gnomad4 AMR AF: 0.00479

Gnomad4 ASJ AF: 0.0256

Gnomad4 EAS AF: 0.000434

Gnomad4 SAS AF: 0.0192

Gnomad4 FIN AF: 0.00378

Gnomad4 NFE AF: 0.0138

Gnomad4 OTH AF: 0.0105

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs56278513; hg19: chr18-47455980;