18-49878934-A-G

Variant names:

• chr18-49878934-A-G
• rs2276176
• NM_001080467.3:c.3276+11T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001080467.3(MYO5B):​c.3276+11T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 1,613,030 control chromosomes in the GnomAD database, including 40,786 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.23 (4204 hom., cov: 32)
  • Exomes 𝑓: 0.22 (36582 hom.)
• Consequence: MYO5B NM_001080467.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.0160
• Publications: 8 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 18-49878934-A-G is Benign according to our data. Variant chr18-49878934-A-G is described in ClinVar as Benign. ClinVar VariationId is 327030.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.406 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.3276+11T>C		intron	N/A	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.3276+11T>C		intron	N/A	ENSP00000285039.6	Q9ULV0-1
	MYO5B	ENST00000697219.1		c.3072+11T>C		intron	N/A	ENSP00000513188.1	A0A8V8TM52
	MYO5B	ENST00000908785.1		c.3276+11T>C		intron	N/A	ENSP00000578844.1

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35133 AN: 151574 Hom.: 4200 Cov.: 32

Gnomad AFR AF: 0.241

Gnomad AMI AF: 0.195

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.214

Gnomad EAS AF: 0.421

Gnomad SAS AF: 0.342

Gnomad FIN AF: 0.259

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.199

Gnomad OTH AF: 0.225

GnomAD2 exomes AF: 0.253 AC: 62941 AN: 249086 AF XY: 0.254

Gnomad AFR exome AF: 0.235

Gnomad AMR exome AF: 0.262

Gnomad ASJ exome AF: 0.224

Gnomad EAS exome AF: 0.435

Gnomad FIN exome AF: 0.258

Gnomad NFE exome AF: 0.201

Gnomad OTH exome AF: 0.244

GnomAD4 exome AF: 0.217 AC: 317246 AN: 1461338 Hom.: 36582 Cov.: 34 AF XY: 0.220 AC XY: 160194 AN XY: 726998

African (AFR) AF: 0.235 AC: 7883 AN: 33474

American (AMR) AF: 0.261 AC: 11651 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.223 AC: 5835 AN: 26132

East Asian (EAS) AF: 0.383 AC: 15187 AN: 39682

South Asian (SAS) AF: 0.339 AC: 29278 AN: 86240

European-Finnish (FIN) AF: 0.257 AC: 13720 AN: 53346

Middle Eastern (MID) AF: 0.235 AC: 1354 AN: 5756

European-Non Finnish (NFE) AF: 0.197 AC: 218447 AN: 1111650

Other (OTH) AF: 0.230 AC: 13891 AN: 60358

GnomAD4 genome AF: 0.232 AC: 35168 AN: 151692 Hom.: 4204 Cov.: 32 AF XY: 0.238 AC XY: 17630 AN XY: 74120

African (AFR) AF: 0.241 AC: 9971 AN: 41324

American (AMR) AF: 0.244 AC: 3713 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.214 AC: 740 AN: 3466

East Asian (EAS) AF: 0.421 AC: 2166 AN: 5142

South Asian (SAS) AF: 0.343 AC: 1643 AN: 4796

European-Finnish (FIN) AF: 0.259 AC: 2725 AN: 10504

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.199 AC: 13492 AN: 67910

Other (OTH) AF: 0.227 AC: 477 AN: 2102

Alfa AF: 0.163 Hom.: 472

Bravo AF: 0.230

Asia WGS AF: 0.362 AC: 1258 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	Congenital microvillous atrophy (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.9
DANN	Benign	0.53
PhyloP100		-0.016
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs2276176; hg19: chr18-47405304;