rs397841722

Variant names:

• chr18-49879055-T-TGAG
• rs397841722
• NM_001080467.3:c.3163_3165dupCTC

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 1P and 16B. PM4_Supporting BP6_Very_Strong BA1

The NM_001080467.3(MYO5B):​c.3163_3165dupCTC​(p.Leu1055dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 1,613,342 control chromosomes in the GnomAD database, including 78,462 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.32 (8240 hom., cov: 0)
  • Exomes 𝑓: 0.30 (70222 hom.)
• Consequence: MYO5B NM_001080467.3 conservative_inframe_insertion
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts P:1 B:6
• Conservation: PhyloP100: -0.226
• Publications: 9 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, 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 -15 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_001080467.3. Strenght limited to Supporting due to length of the change: 1aa.
• BP6: Variant 18-49879055-T-TGAG is Benign according to our data. Variant chr18-49879055-T-TGAG is described in ClinVar as Benign. ClinVar VariationId is 327031.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.526 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080467.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO5B	NM_001080467.3	MANE Select	c.3163_3165dupCTC	p.Leu1055dup	conservative_inframe_insertion	Exon 24 of 40	NP_001073936.1	Q9ULV0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO5B	ENST00000285039.12	TSL:1 MANE Select	c.3163_3165dupCTC	p.Leu1055dup	conservative_inframe_insertion	Exon 24 of 40	ENSP00000285039.6	Q9ULV0-1
	MYO5B	ENST00000697219.1		c.2959_2961dupCTC	p.Leu987dup	conservative_inframe_insertion	Exon 22 of 38	ENSP00000513188.1	A0A8V8TM52
	MYO5B	ENST00000908785.1		c.3163_3165dupCTC	p.Leu1055dup	conservative_inframe_insertion	Exon 24 of 28	ENSP00000578844.1

Frequencies

GnomAD3 genomes AF: 0.324 AC: 49135 AN: 151762 Hom.: 8235 Cov.: 0

Gnomad AFR AF: 0.363

Gnomad AMI AF: 0.273

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.542

Gnomad SAS AF: 0.501

Gnomad FIN AF: 0.365

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.279

Gnomad OTH AF: 0.291

GnomAD2 exomes AF: 0.340 AC: 84825 AN: 249362 AF XY: 0.346

Gnomad AFR exome AF: 0.359

Gnomad AMR exome AF: 0.286

Gnomad ASJ exome AF: 0.281

Gnomad EAS exome AF: 0.557

Gnomad FIN exome AF: 0.364

Gnomad NFE exome AF: 0.280

Gnomad OTH exome AF: 0.316

GnomAD4 exome AF: 0.302 AC: 441199 AN: 1461462 Hom.: 70222 Cov.: 34 AF XY: 0.308 AC XY: 223571 AN XY: 727058

African (AFR) AF: 0.363 AC: 12160 AN: 33470

American (AMR) AF: 0.286 AC: 12806 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.278 AC: 7271 AN: 26134

East Asian (EAS) AF: 0.496 AC: 19681 AN: 39696

South Asian (SAS) AF: 0.493 AC: 42508 AN: 86240

European-Finnish (FIN) AF: 0.363 AC: 19372 AN: 53398

Middle Eastern (MID) AF: 0.322 AC: 1857 AN: 5768

European-Non Finnish (NFE) AF: 0.276 AC: 306608 AN: 1111656

Other (OTH) AF: 0.314 AC: 18936 AN: 60378

GnomAD4 genome AF: 0.324 AC: 49182 AN: 151880 Hom.: 8240 Cov.: 0 AF XY: 0.331 AC XY: 24575 AN XY: 74234

African (AFR) AF: 0.363 AC: 15017 AN: 41390

American (AMR) AF: 0.282 AC: 4311 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.263 AC: 914 AN: 3470

East Asian (EAS) AF: 0.542 AC: 2791 AN: 5146

South Asian (SAS) AF: 0.501 AC: 2409 AN: 4810

European-Finnish (FIN) AF: 0.365 AC: 3843 AN: 10530

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.279 AC: 18951 AN: 67940

Other (OTH) AF: 0.293 AC: 618 AN: 2112

Alfa AF: 0.296 Hom.: 4046

Bravo AF: 0.315

Asia WGS AF: 0.484 AC: 1683 AN: 3478

EpiCase AF: 0.272

EpiControl AF: 0.270

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
1	-	1	Congenital microvillous atrophy (2)
-	-	2	not provided (2)
-	-	1	Congenital microvillous atrophy;C5676981:Cholestasis, progressive familial intrahepatic, 10 (1)
-	-	1	Diarrhea with Microvillus Atrophy (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.23
Mutation Taster		=72/28	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs397841722; hg19: chr18-47405425; COSMIC: COSV53210186; COSMIC: COSV53210186;