dbSNP rs669350: MYO5B:c.4222-447G>T (chr18-49850107-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001080467.3(MYO5B):c.4222-447G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.431 in 277,146 control chromosomes in the GnomAD database, including 27,357 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.44 ( 15326 hom., cov: 33)

Exomes 𝑓: 0.42 ( 12031 hom. )

Consequence

MYO5B
NM_001080467.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.669

Publications

4 publications found

Variant links:

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 links:

SNHG22 (HGNC:50285): (small nucleolar RNA host gene 22)

SNHG22 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.487 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.4222-447G>T		intron	N/A	NP_001073936.1	Q9ULV0-1
	SNHG22	NR_117096.1		n.663C>A		non_coding_transcript_exon	Exon 4 of 4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MYO5B	ENST00000285039.12	TSL:1 MANE Select	c.4222-447G>T	intron	N/A	ENSP00000285039.6	Q9ULV0-1
MYO5B	ENST00000697219.1		c.3955-447G>T	intron	N/A	ENSP00000513188.1	A0A8V8TM52
MYO5B	ENST00000908785.1		c.3603+22060G>T	intron	N/A	ENSP00000578844.1

Frequencies

GnomAD3 genomes

AF:

0.441

AC:

66940

AN:

151926

Hom.:

15328

Cov.:

show subpopulations

Gnomad AFR

AF:

0.437

Gnomad AMI

AF:

0.667

Gnomad AMR

AF:

0.369

Gnomad ASJ

AF:

0.554

Gnomad EAS

AF:

0.116

Gnomad SAS

AF:

0.288

Gnomad FIN

AF:

0.397

Gnomad MID

AF:

0.532

Gnomad NFE

AF:

0.491

Gnomad OTH

AF:

0.474

GnomAD4 exome

AF:

0.419

AC:

52372

AN:

125102

Hom.:

12031

Cov.:

AF XY:

0.406

AC XY:

26825

AN XY:

66090

show subpopulations

African (AFR)

AF:

0.439

AC:

1711

AN:

3898

American (AMR)

AF:

0.303

AC:

1725

AN:

5692

Ashkenazi Jewish (ASJ)

AF:

0.531

AC:

1526

AN:

2874

East Asian (EAS)

AF:

0.106

AC:

631

AN:

5928

South Asian (SAS)

AF:

0.290

AC:

5869

AN:

20216

European-Finnish (FIN)

AF:

0.380

AC:

2203

AN:

5794

Middle Eastern (MID)

AF:

0.456

AC:

216

AN:

474

European-Non Finnish (NFE)

AF:

0.484

AC:

35683

AN:

73780

Other (OTH)

AF:

0.436

AC:

2808

AN:

6446

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1337

2674

4011

5348

6685

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

222

444

666

888

1110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.440

AC:

66952

AN:

152044

Hom.:

15326

Cov.:

AF XY:

0.432

AC XY:

32129

AN XY:

74314

show subpopulations

African (AFR)

AF:

0.437

AC:

18098

AN:

41450

American (AMR)

AF:

0.368

AC:

5632

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.554

AC:

1919

AN:

3464

East Asian (EAS)

AF:

0.115

AC:

596

AN:

5182

South Asian (SAS)

AF:

0.288

AC:

1384

AN:

4808

European-Finnish (FIN)

AF:

0.397

AC:

4206

AN:

10598

Middle Eastern (MID)

AF:

0.538

AC:

157

AN:

292

European-Non Finnish (NFE)

AF:

0.491

AC:

33363

AN:

67948

Other (OTH)

AF:

0.470

AC:

993

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1900

3800

5700

7600

9500

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

608

1216

1824

2432

3040

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.449

Hom.:

2719

Bravo

AF:

0.439

Asia WGS

AF:

0.249

AC:

867

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.43

(source)

DANN

Benign

0.75

PhyloP100

-0.67

PromoterAI

-0.0072

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over