chr18-49962255-A-G

Variant names:

• chr18-49962255-A-G
• rs17715416
• NM_001080467.3:c.1545+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.1545+11T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 1,613,492 control chromosomes in the GnomAD database, including 119,175 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.34 (9231 hom., cov: 32)
  • Exomes 𝑓: 0.38 (109944 hom.)
• Consequence: MYO5B NM_001080467.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.0220
• 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, 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 18-49962255-A-G is Benign according to our data. Variant chr18-49962255-A-G is described in ClinVar as Benign. ClinVar VariationId is 327063.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.499 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO5B	NM_001080467.3	MANE Select	c.1545+11T>C		intron	N/A	NP_001073936.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO5B	ENST00000285039.12	TSL:1 MANE Select	c.1545+11T>C		intron	N/A	ENSP00000285039.6
	MYO5B	ENST00000697219.1		c.1341+11T>C		intron	N/A	ENSP00000513188.1
	MYO5B	ENST00000908785.1		c.1545+11T>C		intron	N/A	ENSP00000578844.1

Frequencies

GnomAD3 genomes AF: 0.335 AC: 50978 AN: 151988 Hom.: 9229 Cov.: 32

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.262

Gnomad AMR AF: 0.415

Gnomad ASJ AF: 0.355

Gnomad EAS AF: 0.259

Gnomad SAS AF: 0.516

Gnomad FIN AF: 0.322

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.393

Gnomad OTH AF: 0.345

GnomAD2 exomes AF: 0.387 AC: 96556 AN: 249440 AF XY: 0.395

Gnomad AFR exome AF: 0.192

Gnomad AMR exome AF: 0.481

Gnomad ASJ exome AF: 0.362

Gnomad EAS exome AF: 0.253

Gnomad FIN exome AF: 0.319

Gnomad NFE exome AF: 0.386

Gnomad OTH exome AF: 0.379

GnomAD4 exome AF: 0.383 AC: 560248 AN: 1461386 Hom.: 109944 Cov.: 41 AF XY: 0.389 AC XY: 282536 AN XY: 727022

African (AFR) AF: 0.191 AC: 6395 AN: 33476

American (AMR) AF: 0.476 AC: 21288 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.355 AC: 9271 AN: 26128

East Asian (EAS) AF: 0.270 AC: 10728 AN: 39690

South Asian (SAS) AF: 0.521 AC: 44922 AN: 86242

European-Finnish (FIN) AF: 0.320 AC: 17081 AN: 53418

Middle Eastern (MID) AF: 0.440 AC: 2536 AN: 5766

European-Non Finnish (NFE) AF: 0.383 AC: 425620 AN: 1111564

Other (OTH) AF: 0.371 AC: 22407 AN: 60378

GnomAD4 genome AF: 0.335 AC: 50998 AN: 152106 Hom.: 9231 Cov.: 32 AF XY: 0.339 AC XY: 25181 AN XY: 74344

African (AFR) AF: 0.203 AC: 8436 AN: 41518

American (AMR) AF: 0.415 AC: 6343 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.355 AC: 1231 AN: 3470

East Asian (EAS) AF: 0.259 AC: 1341 AN: 5174

South Asian (SAS) AF: 0.516 AC: 2480 AN: 4806

European-Finnish (FIN) AF: 0.322 AC: 3403 AN: 10566

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.393 AC: 26681 AN: 67976

Other (OTH) AF: 0.344 AC: 727 AN: 2116

Alfa AF: 0.336 Hom.: 2721

Bravo AF: 0.330

Asia WGS AF: 0.363 AC: 1263 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.0
DANN	Benign	0.70
PhyloP100		-0.022
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: rs17715416; hg19: chr18-47488625; COSMIC: COSV53214173;