rs7960736

Positions:

• chr12-117823483-A-C
• chr12-117823483-A-T

Variant summary

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

The NM_173598.6(KSR2):​c.472+31945T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.455 in 151,942 control chromosomes in the GnomAD database, including 16,207 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 0.45 (16207 hom., cov: 31)
• Consequence: KSR2 NM_173598.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.705

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=-1.08).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.549 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KSR2	NM_173598.6	c.472+31945T>G		intron_variant		ENST00000339824.7	NP_775869.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KSR2	ENST00000339824.7	c.472+31945T>G		intron_variant		5	NM_173598.6	ENSP00000339952	P1

Frequencies

GnomAD3 genomes AF: 0.455 AC: 69005 AN: 151824 Hom.: 16176 Cov.: 31

Gnomad AFR AF: 0.555

Gnomad AMI AF: 0.543

Gnomad AMR AF: 0.455

Gnomad ASJ AF: 0.454

Gnomad EAS AF: 0.327

Gnomad SAS AF: 0.347

Gnomad FIN AF: 0.425

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.413

Gnomad OTH AF: 0.484

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

GnomAD4 genome AF: 0.455 AC: 69084 AN: 151942 Hom.: 16207 Cov.: 31 AF XY: 0.453 AC XY: 33616 AN XY: 74240

Gnomad4 AFR AF: 0.555

Gnomad4 AMR AF: 0.455

Gnomad4 ASJ AF: 0.454

Gnomad4 EAS AF: 0.328

Gnomad4 SAS AF: 0.347

Gnomad4 FIN AF: 0.425

Gnomad4 NFE AF: 0.413

Gnomad4 OTH AF: 0.481

Alfa AF: 0.422 Hom.: 19769

Bravo AF: 0.466

Asia WGS AF: 0.332 AC: 1155 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.62
DANN	Benign	0.30

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: rs7960736; hg19: chr12-118261288;