rs481745

Positions:

• chr12-117671566-C-T

Variant summary

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

The NM_173598.6(KSR2):​c.987-3908G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.389 in 152,178 control chromosomes in the GnomAD database, including 14,046 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 0.39 (14046 hom., cov: 33)
• Consequence: KSR2 NM_173598.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50

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=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.528 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KSR2	NM_173598.6	c.987-3908G>A		intron_variant		ENST00000339824.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KSR2	ENST00000339824.7	c.987-3908G>A		intron_variant		5	NM_173598.6	P1
KSR2	ENST00000545002.1	n.132+2717G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.389 AC: 59155 AN: 152060 Hom.: 14039 Cov.: 33

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.470

Gnomad AMR AF: 0.397

Gnomad ASJ AF: 0.553

Gnomad EAS AF: 0.329

Gnomad SAS AF: 0.476

Gnomad FIN AF: 0.453

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.532

Gnomad OTH AF: 0.426

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

GnomAD4 genome AF: 0.389 AC: 59165 AN: 152178 Hom.: 14046 Cov.: 33 AF XY: 0.389 AC XY: 28907 AN XY: 74394

Gnomad4 AFR AF: 0.113

Gnomad4 AMR AF: 0.397

Gnomad4 ASJ AF: 0.553

Gnomad4 EAS AF: 0.328

Gnomad4 SAS AF: 0.477

Gnomad4 FIN AF: 0.453

Gnomad4 NFE AF: 0.532

Gnomad4 OTH AF: 0.432

Alfa AF: 0.507 Hom.: 33889

Bravo AF: 0.366

Asia WGS AF: 0.394 AC: 1371 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.098
DANN	Benign	0.42

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: rs481745; hg19: chr12-118109371;