Genetic Variant NM_032608.7:c.4225-90G>A (chr22-25877869-G-A) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2

The NM_032608.7(MYO18B):c.4225-90G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0281 in 975,484 control chromosomes in the GnomAD database, including 509 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

Frequency

Genomes: 𝑓 0.023 ( 48 hom., cov: 33)

Exomes 𝑓: 0.029 ( 461 hom. )

Consequence

MYO18B
NM_032608.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.21

Publications

3 publications found

Variant links:

Genes affected

MYO18B (HGNC:18150): (myosin XVIIIB) The protein encoded by this gene may regulate muscle-specific genes when in the nucleus and may influence intracellular trafficking when in the cytoplasm. The encoded protein functions as a homodimer and may interact with F actin. Mutations in this gene are associated with lung cancer. [provided by RefSeq, Jul 2008]

MYO18B links:

MYO18B-AS1 (HGNC:40831): (MYO18B antisense RNA 1)

MYO18B-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0228 (3468/151962) while in subpopulation NFE AF = 0.0356 (2421/67926). AF 95% confidence interval is 0.0345. There are 48 homozygotes in GnomAd4. There are 1585 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High Homozygotes in GnomAd4 at 48 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032608.7. 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
	MYO18B	NM_032608.7	MANE Select	c.4225-90G>A		intron	N/A	NP_115997.5
	MYO18B	NM_001318245.2		c.4228-90G>A		intron	N/A	NP_001305174.1	Q8IUG5-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MYO18B	ENST00000335473.12	TSL:1 MANE Select	c.4225-90G>A	intron	N/A	ENSP00000334563.8	Q8IUG5-1
MYO18B	ENST00000407587.6	TSL:1	c.4228-90G>A	intron	N/A	ENSP00000386096.2	Q8IUG5-3
MYO18B	ENST00000536101.5	TSL:1	c.4225-90G>A	intron	N/A	ENSP00000441229.1	Q8IUG5-1

Frequencies

GnomAD3 genomes

AF:

0.0228

AC:

3469

AN:

151842

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00641

Gnomad AMI

AF:

0.0703

Gnomad AMR

AF:

0.0258

Gnomad ASJ

AF:

0.0251

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00270

Gnomad FIN

AF:

0.0143

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.0357

Gnomad OTH

AF:

0.0339

GnomAD4 exome

AF:

0.0291

AC:

23973

AN:

823522

Hom.:

461

AF XY:

0.0281

AC XY:

11849

AN XY:

421944

show subpopulations

African (AFR)

AF:

0.00644

AC:

128

AN:

19882

American (AMR)

AF:

0.0202

AC:

579

AN:

28726

Ashkenazi Jewish (ASJ)

AF:

0.0302

AC:

576

AN:

19076

East Asian (EAS)

AF:

0.0000312

AC:

AN:

32092

South Asian (SAS)

AF:

0.00169

AC:

100

AN:

59276

European-Finnish (FIN)

AF:

0.0174

AC:

817

AN:

46992

Middle Eastern (MID)

AF:

0.00722

AC:

AN:

4432

European-Non Finnish (NFE)

AF:

0.0360

AC:

20662

AN:

574684

Other (OTH)

AF:

0.0281

AC:

1078

AN:

38362

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1113

2226

3338

4451

5564

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

560

1120

1680

2240

2800

<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:

0.0228

AC:

3468

AN:

151962

Hom.:

Cov.:

AF XY:

0.0213

AC XY:

1585

AN XY:

74268

show subpopulations

African (AFR)

AF:

0.00639

AC:

265

AN:

41444

American (AMR)

AF:

0.0258

AC:

394

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.0251

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00270

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.0143

AC:

151

AN:

10526

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0356

AC:

2421

AN:

67926

Other (OTH)

AF:

0.0336

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

175

349

524

698

873

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

126

168

210

<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:

0.00429

Hom.:

1734

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.63

(source)

DANN

Benign

0.96

PhyloP100

-1.2

Mutation Taster

=100/0

polymorphism

(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