18-49929610-GAAAAAAA-GAAA

Variant names:

• chr18-49929610-GAAAA-G
• rs56278513
• NM_001080467.3:c.2004-16_2004-13delTTTT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001080467.3(MYO5B):​c.2004-16_2004-13delTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000469 in 1,283,204 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 0.000015 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00052 (0 hom.)
• Consequence: MYO5B NM_001080467.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.06
• Publications: 2 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: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.0000151 AC: 2 AN: 132858 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000282

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000308

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000848 AC: 97 AN: 114366 AF XY: 0.000713

Gnomad AFR exome AF: 0.000643

Gnomad AMR exome AF: 0.00122

Gnomad ASJ exome AF: 0.000161

Gnomad EAS exome AF: 0.000813

Gnomad FIN exome AF: 0.00213

Gnomad NFE exome AF: 0.000779

Gnomad OTH exome AF: 0.000307

GnomAD4 exome AF: 0.000522 AC: 600 AN: 1150346 Hom.: 0 AF XY: 0.000509 AC XY: 293 AN XY: 575230

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000830 AC: 22 AN: 26510

American (AMR) AF: 0.000782 AC: 25 AN: 31970

Ashkenazi Jewish (ASJ) AF: 0.000542 AC: 12 AN: 22160

East Asian (EAS) AF: 0.000210 AC: 7 AN: 33404

South Asian (SAS) AF: 0.000442 AC: 31 AN: 70210

European-Finnish (FIN) AF: 0.000665 AC: 24 AN: 36086

Middle Eastern (MID) AF: 0.000285 AC: 1 AN: 3504

European-Non Finnish (NFE) AF: 0.000520 AC: 456 AN: 877674

Other (OTH) AF: 0.000451 AC: 22 AN: 48828

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000151 AC: 2 AN: 132858 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 63436

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000282 AC: 1 AN: 35426

American (AMR) AF: 0.00 AC: 0 AN: 13132

Ashkenazi Jewish (ASJ) AF: 0.000308 AC: 1 AN: 3244

East Asian (EAS) AF: 0.00 AC: 0 AN: 4620

South Asian (SAS) AF: 0.00 AC: 0 AN: 4086

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6888

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 284

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 62530

Other (OTH) AF: 0.00 AC: 0 AN: 1808

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00721 Hom.: 142

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.1
Mutation Taster		=100/0	polymorphism

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: rs56278513; hg19: chr18-47455980;