ENST00000510199.5:c.253+1271C>A

Variant names:

• chr5-181245853-G-T
• rs10078827
• ENST00000510199.5:c.253+1271C>A

Variant summary

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

The ENST00000510199.5(RACK1):​c.253+1271C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 152,218 control chromosomes in the GnomAD database, including 1,727 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 0.12 (1727 hom., cov: 33)
• Consequence: RACK1 ENST00000510199.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.876
• Publications: 4 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.267 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000510199.5. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RACK1	ENST00000510199.5	TSL:3	c.253+1271C>A		intron	N/A	ENSP00000423569.1	D6R9L0
	RACK1	ENST00000507000.5	TSL:5	c.-15+2156C>A		intron	N/A	ENSP00000421416.1	D6RFX4

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18434 AN: 152100 Hom.: 1716 Cov.: 33

Gnomad AFR AF: 0.240

Gnomad AMI AF: 0.0822

Gnomad AMR AF: 0.0946

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.278

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.0819

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.0451

Gnomad OTH AF: 0.121

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.121 AC: 18490 AN: 152218 Hom.: 1727 Cov.: 33 AF XY: 0.124 AC XY: 9231 AN XY: 74438

African (AFR) AF: 0.240 AC: 9973 AN: 41490

American (AMR) AF: 0.0947 AC: 1450 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 512 AN: 3466

East Asian (EAS) AF: 0.279 AC: 1440 AN: 5166

South Asian (SAS) AF: 0.163 AC: 786 AN: 4828

European-Finnish (FIN) AF: 0.0819 AC: 870 AN: 10622

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

European-Non Finnish (NFE) AF: 0.0451 AC: 3069 AN: 68022

Other (OTH) AF: 0.120 AC: 253 AN: 2114

Alfa AF: 0.0912 Hom.: 1160

Bravo AF: 0.130

Asia WGS AF: 0.233 AC: 810 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.3
DANN	Benign	0.63
PhyloP100		-0.88

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs10078827;

hg19: chr5-180672853;