18-49929610-GAAAAAAA-GAAAA

Variant names:

• chr18-49929610-GAAA-G
• rs56278513
• NM_001080467.3:c.2004-15_2004-13delTTT

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BS1

The NM_001080467.3(MYO5B):​c.2004-15_2004-13delTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00436 in 1,260,590 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000060 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0049 (0 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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BS1: Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.00487 (5489/1127764) while in subpopulation AMR AF= 0.00723 (227/31410). AF 95% confidence interval is 0.00646. There are 0 homozygotes in gnomad4_exome. There are 2565 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO5B	NM_001080467.3	c.2004-15_2004-13delTTT		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.2004-15_2004-13delTTT		intron_variant	Intron 16 of 39	1	NM_001080467.3	ENSP00000285039.6
MYO5B	ENST00000697219.1	c.1800-15_1800-13delTTT		intron_variant	Intron 14 of 37			ENSP00000513188.1

Frequencies

GnomAD3 genomes AF: 0.0000602 AC: 8 AN: 132848 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000565

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000152

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000145

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000480

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00734 AC: 840 AN: 114366 Hom.: 0 AF XY: 0.00712 AC XY: 439 AN XY: 61680

Gnomad AFR exome AF: 0.00579

Gnomad AMR exome AF: 0.00885

Gnomad ASJ exome AF: 0.00402

Gnomad EAS exome AF: 0.00755

Gnomad SAS exome AF: 0.00679

Gnomad FIN exome AF: 0.0137

Gnomad NFE exome AF: 0.00661

Gnomad OTH exome AF: 0.00675

GnomAD4 exome AF: 0.00487 AC: 5489 AN: 1127764 Hom.: 0 AF XY: 0.00455 AC XY: 2565 AN XY: 563876

Gnomad4 AFR exome AF: 0.00531

Gnomad4 AMR exome AF: 0.00723

Gnomad4 ASJ exome AF: 0.00378

Gnomad4 EAS exome AF: 0.00341

Gnomad4 SAS exome AF: 0.00421

Gnomad4 FIN exome AF: 0.00467

Gnomad4 NFE exome AF: 0.00492

Gnomad4 OTH exome AF: 0.00475

GnomAD4 genome AF: 0.0000602 AC: 8 AN: 132826 Hom.: 0 Cov.: 0 AF XY: 0.0000630 AC XY: 4 AN XY: 63444

Gnomad4 AFR AF: 0.0000564

Gnomad4 AMR AF: 0.000152

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000145

Gnomad4 NFE AF: 0.0000480

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs56278513; hg19: chr18-47455980;