12-117823483-A-C

Variant names:

• chr12-117823483-A-C
• rs7960736
• NM_173598.6:c.472+31945T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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=-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 rank	MANE	Protein	UniProt
KSR2	NM_173598.6	c.472+31945T>G		intron_variant	Intron 3 of 19	ENST00000339824.7	NP_775869.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KSR2	ENST00000339824.7	c.472+31945T>G		intron_variant	Intron 3 of 19	5	NM_173598.6	ENSP00000339952.4

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

African (AFR) AF: 0.555 AC: 22990 AN: 41404

American (AMR) AF: 0.455 AC: 6938 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.454 AC: 1575 AN: 3466

East Asian (EAS) AF: 0.328 AC: 1694 AN: 5170

South Asian (SAS) AF: 0.347 AC: 1672 AN: 4818

European-Finnish (FIN) AF: 0.425 AC: 4488 AN: 10550

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.413 AC: 28074 AN: 67962

Other (OTH) AF: 0.481 AC: 1014 AN: 2108

Alfa AF: 0.428 Hom.: 30495

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
PhyloP100		-0.70
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: rs7960736; hg19: chr12-118261288;