NM_001080467.3:c.3396+9T>C

Variant names:

• chr18-49877754-A-G
• rs75971548
• NM_001080467.3:c.3396+9T>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.3396+9T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0549 in 1,613,816 control chromosomes in the GnomAD database, including 3,302 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.042 (177 hom., cov: 32)
  • Exomes 𝑓: 0.056 (3125 hom.)
• Consequence: MYO5B NM_001080467.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.0720
• Publications: 3 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=-0.82).
• BP6: Variant 18-49877754-A-G is Benign according to our data. Variant chr18-49877754-A-G is described in ClinVar as Benign. ClinVar VariationId is 327028.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.147 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.3396+9T>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.3396+9T>C		intron	N/A	ENSP00000285039.6	Q9ULV0-1
	MYO5B	ENST00000697219.1		c.3192+9T>C		intron	N/A	ENSP00000513188.1	A0A8V8TM52
	MYO5B	ENST00000908785.1		c.3396+9T>C		intron	N/A	ENSP00000578844.1

Frequencies

GnomAD3 genomes AF: 0.0422 AC: 6423 AN: 152170 Hom.: 177 Cov.: 32

Gnomad AFR AF: 0.0217

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0272

Gnomad ASJ AF: 0.0617

Gnomad EAS AF: 0.00655

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.0602

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0494

Gnomad OTH AF: 0.0406

GnomAD2 exomes AF: 0.0576 AC: 14368 AN: 249398 AF XY: 0.0644

Gnomad AFR exome AF: 0.0201

Gnomad AMR exome AF: 0.0221

Gnomad ASJ exome AF: 0.0698

Gnomad EAS exome AF: 0.00506

Gnomad FIN exome AF: 0.0606

Gnomad NFE exome AF: 0.0504

Gnomad OTH exome AF: 0.0578

GnomAD4 exome AF: 0.0562 AC: 82162 AN: 1461528 Hom.: 3125 Cov.: 32 AF XY: 0.0600 AC XY: 43630 AN XY: 727072

African (AFR) AF: 0.0219 AC: 734 AN: 33462

American (AMR) AF: 0.0229 AC: 1026 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.0697 AC: 1821 AN: 26130

East Asian (EAS) AF: 0.00348 AC: 138 AN: 39686

South Asian (SAS) AF: 0.164 AC: 14184 AN: 86248

European-Finnish (FIN) AF: 0.0617 AC: 3293 AN: 53410

Middle Eastern (MID) AF: 0.0712 AC: 409 AN: 5744

European-Non Finnish (NFE) AF: 0.0514 AC: 57138 AN: 1111764

Other (OTH) AF: 0.0566 AC: 3419 AN: 60366

GnomAD4 genome AF: 0.0422 AC: 6428 AN: 152288 Hom.: 177 Cov.: 32 AF XY: 0.0447 AC XY: 3328 AN XY: 74450

African (AFR) AF: 0.0218 AC: 907 AN: 41566

American (AMR) AF: 0.0271 AC: 415 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0617 AC: 214 AN: 3468

East Asian (EAS) AF: 0.00656 AC: 34 AN: 5182

South Asian (SAS) AF: 0.156 AC: 751 AN: 4820

European-Finnish (FIN) AF: 0.0602 AC: 639 AN: 10614

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0494 AC: 3357 AN: 68020

Other (OTH) AF: 0.0397 AC: 84 AN: 2114

Alfa AF: 0.0483 Hom.: 97

Bravo AF: 0.0370

Asia WGS AF: 0.0870 AC: 304 AN: 3478

EpiCase AF: 0.0527

EpiControl AF: 0.0511

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	-0.82
CADD	Benign	8.3
DANN	Benign	0.38
PhyloP100		0.072
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: rs75971548; hg19: chr18-47404124;