rs4304868

Positions:

• chr12-117732104-C-A
• chr12-117732104-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_173598.6(KSR2):​c.986+28907G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 151,656 control chromosomes in the GnomAD database, including 3,003 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 0.19 (3003 hom., cov: 30)
• Consequence: KSR2 NM_173598.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10

Genes affected

KSR2 (HGNC:18610): (kinase suppressor of ras 2) Predicted to enable MAP-kinase scaffold activity; mitogen-activated protein kinase kinase binding activity; and protein kinase activity. Predicted to be involved in Ras protein signal transduction; calcium-mediated signaling; and positive regulation of cold-induced thermogenesis. Predicted to act upstream of or within positive regulation of MAPK cascade. Predicted to be active in cytosol and plasma membrane. [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=-0.99).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KSR2	NM_173598.6	c.986+28907G>T		intron_variant		ENST00000339824.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KSR2	ENST00000339824.7	c.986+28907G>T		intron_variant		5	NM_173598.6	P1

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29375 AN: 151540 Hom.: 3003 Cov.: 30

Gnomad AFR AF: 0.214

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.228

Gnomad EAS AF: 0.215

Gnomad SAS AF: 0.296

Gnomad FIN AF: 0.192

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.183

Gnomad OTH AF: 0.210

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

GnomAD4 genome AF: 0.194 AC: 29387 AN: 151656 Hom.: 3003 Cov.: 30 AF XY: 0.193 AC XY: 14312 AN XY: 74064

Gnomad4 AFR AF: 0.214

Gnomad4 AMR AF: 0.140

Gnomad4 ASJ AF: 0.228

Gnomad4 EAS AF: 0.215

Gnomad4 SAS AF: 0.295

Gnomad4 FIN AF: 0.192

Gnomad4 NFE AF: 0.183

Gnomad4 OTH AF: 0.216

Alfa AF: 0.177 Hom.: 2789

Bravo AF: 0.189

Asia WGS AF: 0.227 AC: 790 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.039
DANN	Benign	0.40

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

Publications

LitVar

Other links and lift over

dbSNP: rs4304868; hg19: chr12-118169909;