rs4304868

Variant names:

• chr12-117732104-C-A
• rs4304868
• NM_173598.6:c.986+28907G>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
KSR2	NM_173598.6	c.986+28907G>T		intron_variant	Intron 4 of 19	ENST00000339824.7	NP_775869.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KSR2	ENST00000339824.7	c.986+28907G>T		intron_variant	Intron 4 of 19	5	NM_173598.6	ENSP00000339952.4

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

African (AFR) AF: 0.214 AC: 8841 AN: 41350

American (AMR) AF: 0.140 AC: 2132 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.228 AC: 791 AN: 3470

East Asian (EAS) AF: 0.215 AC: 1106 AN: 5134

South Asian (SAS) AF: 0.295 AC: 1415 AN: 4794

European-Finnish (FIN) AF: 0.192 AC: 2002 AN: 10432

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.183 AC: 12437 AN: 67922

Other (OTH) AF: 0.216 AC: 457 AN: 2114

Alfa AF: 0.183 Hom.: 8149

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
PhyloP100		-1.1
Mutation Taster		=100/0	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: rs4304868; hg19: chr12-118169909;