Genetic Variant RACK1:c.-28C>G (chr5-181248022-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000507000.5(RACK1):c.-28C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.432 in 152,230 control chromosomes in the GnomAD database, including 19,375 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 0.43 ( 19373 hom., cov: 33)

Exomes 𝑓: 0.28 ( 2 hom. )

Consequence

RACK1
ENST00000507000.5 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.375

Publications

9 publications found

Variant links:

Genes affected

RACK1 (HGNC:4399): (receptor for activated C kinase 1) Enables several functions, including cyclin binding activity; enzyme binding activity; and protein domain specific binding activity. Involved in several processes, including positive regulation of hydrolase activity; regulation of cellular protein metabolic process; and regulation of signal transduction. Located in several cellular components, including midbody; perinuclear region of cytoplasm; and phagocytic cup. Part of IRE1-RACK1-PP2A complex. [provided by Alliance of Genome Resources, Apr 2022]

RACK1 links:

TRIM52-AS1 (HGNC:49006): (TRIM52 antisense RNA 1 (head to head))

TRIM52-AS1 links:

CTC-338M12.4 (HGNC:):

CTC-338M12.4 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=-1.01).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.839 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTC-338M12.4	NR_109909.1 link	n.613+636G>C		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein
RACK1	ENST00000507000.5 link	c.-28C>G	5_prime_UTR_variant	Exon 1 of 6	5	ENSP00000421416.1
TRIM52-AS1	ENST00000715342.2 link	n.924+636G>C	intron_variant	Intron 1 of 1
TRIM52-AS1	ENST00000715343.2 link	n.688+636G>C	intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.432

AC:

65619

AN:

152036

Hom.:

19315

Cov.:

show subpopulations

Gnomad AFR

AF:

0.846

Gnomad AMI

AF:

0.265

Gnomad AMR

AF:

0.314

Gnomad ASJ

AF:

0.361

Gnomad EAS

AF:

0.358

Gnomad SAS

AF:

0.389

Gnomad FIN

AF:

0.242

Gnomad MID

AF:

0.443

Gnomad NFE

AF:

0.250

Gnomad OTH

AF:

0.412

GnomAD4 exome

AF:

0.276

AC:

AN:

Hom.:

Cov.:

AF XY:

0.280

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.750

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.333

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.233

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.432

AC:

65737

AN:

152154

Hom.:

19373

Cov.:

AF XY:

0.428

AC XY:

31815

AN XY:

74380

show subpopulations

African (AFR)

AF:

0.847

AC:

35170

AN:

41528

American (AMR)

AF:

0.314

AC:

4796

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.361

AC:

1253

AN:

3470

East Asian (EAS)

AF:

0.358

AC:

1855

AN:

5178

South Asian (SAS)

AF:

0.389

AC:

1877

AN:

4824

European-Finnish (FIN)

AF:

0.242

AC:

2561

AN:

10568

Middle Eastern (MID)

AF:

0.446

AC:

131

AN:

294

European-Non Finnish (NFE)

AF:

0.250

AC:

16981

AN:

67996

Other (OTH)

AF:

0.412

AC:

872

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1419

2838

4258

5677

7096

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

534

1068

1602

2136

2670

<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:

0.159

Hom.:

273

Bravo

AF:

0.455

Asia WGS

AF:

0.426

AC:

1484

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

4.0

(source)

DANN

Benign

0.56

PhyloP100

-0.38

PromoterAI

-0.0056

Neutral

(source)

Splicing

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over