5-181242275-C-T

Variant names:

• chr5-181242275-C-T
• rs59085681
• NM_006098.5:c.180G>A

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 1P and 10B. PP3 BP6_Moderate BA1

The NM_006098.5(RACK1):​c.180G>A​(p.Arg60Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0045 in 1,613,564 control chromosomes in the GnomAD database, including 119 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.016 (63 hom., cov: 33)
  • Exomes 𝑓: 0.0033 (56 hom.)
• Consequence: RACK1 NM_006098.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.941
• Publications: 2 publications found

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 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• Tourette syndrome

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

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

• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
• BP6: Variant 5-181242275-C-T is Benign according to our data. Variant chr5-181242275-C-T is described in ClinVar as Benign. ClinVar VariationId is 781742.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0509 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006098.5. 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
	RACK1	NM_006098.5	MANE Select	c.180G>A	p.Arg60Arg	synonymous	Exon 2 of 8	NP_006089.1	P63244

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RACK1	ENST00000512805.6	TSL:1 MANE Select	c.180G>A	p.Arg60Arg	synonymous	Exon 2 of 8	ENSP00000426909.1	P63244
	RACK1	ENST00000376817.8	TSL:5	c.110-62G>A		intron	N/A	ENSP00000366013.4	J3KPE3
	RACK1	ENST00000502548.5	TSL:1	n.296G>A		non_coding_transcript_exon	Exon 2 of 4

Frequencies

GnomAD3 genomes AF: 0.0156 AC: 2377 AN: 152198 Hom.: 62 Cov.: 33

Gnomad AFR AF: 0.0506

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.00497

Gnomad ASJ AF: 0.00806

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00600

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00162

Gnomad OTH AF: 0.00860

GnomAD2 exomes AF: 0.00597 AC: 1500 AN: 251338 AF XY: 0.00529

Gnomad AFR exome AF: 0.0508

Gnomad AMR exome AF: 0.00315

Gnomad ASJ exome AF: 0.0103

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.00187

Gnomad OTH exome AF: 0.00456

GnomAD4 exome AF: 0.00333 AC: 4872 AN: 1461248 Hom.: 56 Cov.: 31 AF XY: 0.00335 AC XY: 2439 AN XY: 726990

African (AFR) AF: 0.0530 AC: 1773 AN: 33452

American (AMR) AF: 0.00333 AC: 149 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0106 AC: 278 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00667 AC: 575 AN: 86248

European-Finnish (FIN) AF: 0.000112 AC: 6 AN: 53418

Middle Eastern (MID) AF: 0.00850 AC: 49 AN: 5768

European-Non Finnish (NFE) AF: 0.00150 AC: 1671 AN: 1111434

Other (OTH) AF: 0.00614 AC: 371 AN: 60376

GnomAD4 genome AF: 0.0157 AC: 2384 AN: 152316 Hom.: 63 Cov.: 33 AF XY: 0.0146 AC XY: 1088 AN XY: 74482

African (AFR) AF: 0.0507 AC: 2106 AN: 41552

American (AMR) AF: 0.00497 AC: 76 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00806 AC: 28 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00580 AC: 28 AN: 4828

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10618

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00162 AC: 110 AN: 68034

Other (OTH) AF: 0.00851 AC: 18 AN: 2114

Alfa AF: 0.0131 Hom.: 34

Bravo AF: 0.0179

Asia WGS AF: 0.00346 AC: 12 AN: 3478

EpiCase AF: 0.00316

EpiControl AF: 0.00344

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	11
DANN	Benign	0.69
PhyloP100		-0.94
PromoterAI		0.071	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.9
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.66		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.66		Position offset: -1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs59085681; hg19: chr5-180669275;