rs3756585

Variant names:

• chr5-181244029-A-C
• rs3756585
• ENST00000889840.1:c.-229T>G

Your query was ambiguous. Multiple possible variants found:

• chr5-181244029-A-C
• chr5-181244029-A-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000889840.1(RACK1):​c.-229T>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 0.0809 in 1,391,956 control chromosomes in the GnomAD database, including 7,053 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 0.13 (1859 hom., cov: 33)
  • Exomes 𝑓: 0.075 (5194 hom.)
• Consequence: RACK1 ENST00000889840.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.54
• Publications: 11 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000889840.1. 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.-229T>G		upstream_gene	N/A	NP_006089.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RACK1	ENST00000889840.1		c.-229T>G		5_prime_UTR	Exon 1 of 6	ENSP00000559899.1
	RACK1	ENST00000510199.5	TSL:3	c.254-1684T>G		intron	N/A	ENSP00000423569.1
	RACK1	ENST00000507000.5	TSL:5	c.-14-1684T>G		intron	N/A	ENSP00000421416.1

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19859 AN: 152194 Hom.: 1843 Cov.: 33

Gnomad AFR AF: 0.244

Gnomad AMI AF: 0.0932

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.270

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.0594

Gnomad OTH AF: 0.129

GnomAD4 exome AF: 0.0748 AC: 92743 AN: 1239644 Hom.: 5194 Cov.: 31 AF XY: 0.0764 AC XY: 45677 AN XY: 597822

African (AFR) AF: 0.254 AC: 6878 AN: 27028

American (AMR) AF: 0.107 AC: 1693 AN: 15766

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 2340 AN: 17926

East Asian (EAS) AF: 0.271 AC: 8545 AN: 31476

South Asian (SAS) AF: 0.153 AC: 8844 AN: 57698

European-Finnish (FIN) AF: 0.0957 AC: 2667 AN: 27866

Middle Eastern (MID) AF: 0.180 AC: 620 AN: 3448

European-Non Finnish (NFE) AF: 0.0556 AC: 55970 AN: 1007198

Other (OTH) AF: 0.101 AC: 5186 AN: 51238

GnomAD4 genome AF: 0.131 AC: 19911 AN: 152312 Hom.: 1859 Cov.: 33 AF XY: 0.133 AC XY: 9908 AN XY: 74470

African (AFR) AF: 0.245 AC: 10188 AN: 41556

American (AMR) AF: 0.101 AC: 1547 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 470 AN: 3468

East Asian (EAS) AF: 0.270 AC: 1397 AN: 5176

South Asian (SAS) AF: 0.161 AC: 779 AN: 4832

European-Finnish (FIN) AF: 0.101 AC: 1076 AN: 10620

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.0593 AC: 4037 AN: 68028

Other (OTH) AF: 0.128 AC: 270 AN: 2116

Alfa AF: 0.114 Hom.: 533

Bravo AF: 0.138

Asia WGS AF: 0.229 AC: 797 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.37
DANN	Benign	0.53
PhyloP100		-3.5
PromoterAI		0.0067	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3756585; hg19: chr5-180671029; COSMIC: COSV65174853; COSMIC: COSV65174853;