Variant chr5-181241646-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_006098.5(RACK1):c.282-7C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00472 in 1,613,818 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0032 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0049 ( 30 hom. )

Consequence

RACK1
NM_006098.5 splice_region, intron

Scores

Splicing: ADA: 0.00002667

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.859

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:

RACK1 (HGNC:):

RACK1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 5-181241646-G-A is Benign according to our data. Variant chr5-181241646-G-A is described in ClinVar as [Benign]. Clinvar id is 774862.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 490 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RACK1	NM_006098.5 linkuse as main transcript	c.282-7C>T		splice_region_variant, intron_variant		ENST00000512805.6	NP_006089.1	P63244E9KL35

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RACK1	ENST00000512805.6 linkuse as main transcript	c.282-7C>T		splice_region_variant, intron_variant		1	NM_006098.5	ENSP00000426909.1		P63244
RACK1	ENST00000376817.8 linkuse as main transcript	c.150-7C>T		splice_region_variant, intron_variant		5		ENSP00000366013.4		J3KPE3

Frequencies

GnomAD3 genomes

AF:

0.00322

AC:

490

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00118

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00216

Gnomad ASJ

AF:

0.00663

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000660

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00534

Gnomad OTH

AF:

0.00574

GnomAD3 exomes

AF:

0.00287

AC:

721

AN:

251104

Hom.:

AF XY:

0.00273

AC XY:

370

AN XY:

135708

show subpopulations

Gnomad AFR exome

AF:

0.00117

Gnomad AMR exome

AF:

0.00197

Gnomad ASJ exome

AF:

0.00616

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.000604

Gnomad NFE exome

AF:

0.00473

Gnomad OTH exome

AF:

0.00343

GnomAD4 exome

AF:

0.00487

AC:

7121

AN:

1461550

Hom.:

Cov.:

AF XY:

0.00472

AC XY:

3431

AN XY:

727094

show subpopulations

Gnomad4 AFR exome

AF:

0.00102

Gnomad4 AMR exome

AF:

0.00199

Gnomad4 ASJ exome

AF:

0.00628

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.000900

Gnomad4 NFE exome

AF:

0.00583

Gnomad4 OTH exome

AF:

0.00490

GnomAD4 genome

AF:

0.00322

AC:

490

AN:

152268

Hom.:

Cov.:

AF XY:

0.00289

AC XY:

215

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.00118

Gnomad4 AMR

AF:

0.00216

Gnomad4 ASJ

AF:

0.00663

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000660

Gnomad4 NFE

AF:

0.00534

Gnomad4 OTH

AF:

0.00568

Alfa

AF:

0.00451

Hom.:

Bravo

AF:

0.00332

EpiCase

AF:

0.00589

EpiControl

AF:

0.00457

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.23

DANN

Benign

0.70

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000027

dbscSNV1_RF

Benign

0.012

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over