Genetic Variant RAB36:c.*119A>G (chr22-23161683-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_004914.5(RAB36):c.*119A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.49 in 868,854 control chromosomes in the GnomAD database, including 105,981 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 0.51 ( 20102 hom., cov: 33)

Exomes 𝑓: 0.49 ( 85879 hom. )

Consequence

RAB36
NM_004914.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.764

Publications

6 publications found

Variant links:

Genes affected

RAB36 (HGNC:9775): (RAB36, member RAS oncogene family) Predicted to enable GTP binding activity and GTPase activity. Predicted to be involved in protein transport. Predicted to be located in Golgi membrane. [provided by Alliance of Genome Resources, Apr 2022]

RAB36 links:

RSPH14 (HGNC:13437): (radial spoke head 14 homolog) This gene encodes a protein with no known function but with slight similarity to a yeast vacuolar protein. The gene is located in a region deleted in pediatric rhabdoid tumors of the brain, kidney and soft tissues, but mutations in this gene have not been associated with the disease. [provided by RefSeq, Jul 2008]

RSPH14 links:

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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=-0.86).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.63 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAB36	NM_004914.5 link	c.*119A>G		3_prime_UTR_variant	Exon 11 of 11	ENST00000263116.8	NP_004905.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAB36	ENST00000263116.8 link	c.*119A>G		3_prime_UTR_variant	Exon 11 of 11	1	NM_004914.5	ENSP00000263116.3
RAB36	ENST00000341989.9 link	c.*119A>G		downstream_gene_variant		1		ENSP00000343494.5

Frequencies

GnomAD3 genomes

AF:

0.512

AC:

77759

AN:

151924

Hom.:

20075

Cov.:

show subpopulations

Gnomad AFR

AF:

0.542

Gnomad AMI

AF:

0.595

Gnomad AMR

AF:

0.478

Gnomad ASJ

AF:

0.486

Gnomad EAS

AF:

0.649

Gnomad SAS

AF:

0.596

Gnomad FIN

AF:

0.436

Gnomad MID

AF:

0.560

Gnomad NFE

AF:

0.497

Gnomad OTH

AF:

0.506

GnomAD4 exome

AF:

0.485

AC:

347785

AN:

716812

Hom.:

85879

Cov.:

AF XY:

0.491

AC XY:

179442

AN XY:

365650

show subpopulations

African (AFR)

AF:

0.512

AC:

9092

AN:

17774

American (AMR)

AF:

0.470

AC:

12582

AN:

26792

Ashkenazi Jewish (ASJ)

AF:

0.480

AC:

7894

AN:

16458

East Asian (EAS)

AF:

0.626

AC:

19517

AN:

31178

South Asian (SAS)

AF:

0.592

AC:

32371

AN:

54676

European-Finnish (FIN)

AF:

0.426

AC:

12606

AN:

29574

Middle Eastern (MID)

AF:

0.525

AC:

1366

AN:

2602

European-Non Finnish (NFE)

AF:

0.468

AC:

235367

AN:

503292

Other (OTH)

AF:

0.493

AC:

16990

AN:

34466

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

7382

14764

22146

29528

36910

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4840

9680

14520

19360

24200

<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:

0.512

AC:

77838

AN:

152042

Hom.:

20102

Cov.:

AF XY:

0.514

AC XY:

38174

AN XY:

74312

show subpopulations

African (AFR)

AF:

0.542

AC:

22491

AN:

41486

American (AMR)

AF:

0.479

AC:

7317

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.486

AC:

1688

AN:

3472

East Asian (EAS)

AF:

0.649

AC:

3330

AN:

5134

South Asian (SAS)

AF:

0.597

AC:

2877

AN:

4820

European-Finnish (FIN)

AF:

0.436

AC:

4602

AN:

10566

Middle Eastern (MID)

AF:

0.551

AC:

162

AN:

294

European-Non Finnish (NFE)

AF:

0.497

AC:

33751

AN:

67960

Other (OTH)

AF:

0.511

AC:

1077

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

2008

4015

6023

8030

10038

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

704

1408

2112

2816

3520

<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:

0.501

Hom.:

7439

Bravo

AF:

0.512

Asia WGS

AF:

0.606

AC:

2109

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

2.4

(source)

DANN

Benign

0.55

PhyloP100

-0.76

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over