5-181245853-G-T

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RACK1	ENST00000510199.5	c.253+1271C>A		intron_variant	Intron 1 of 5	3		ENSP00000423569.1
RACK1	ENST00000507000.5	c.-15+2156C>A		intron_variant	Intron 1 of 5	5		ENSP00000421416.1

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

Gnomad4 AFR AF: 0.240

Gnomad4 AMR AF: 0.0947

Gnomad4 ASJ AF: 0.148

Gnomad4 EAS AF: 0.279

Gnomad4 SAS AF: 0.163

Gnomad4 FIN AF: 0.0819

Gnomad4 NFE AF: 0.0451

Gnomad4 OTH AF: 0.120

Alfa AF: 0.0532 Hom.: 161

Bravo AF: 0.130

Asia WGS AF: 0.233 AC: 810 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10078827; hg19: chr5-180672853;