rs481745

Variant names:

• chr12-117671566-C-T
• rs481745
• NM_173598.6:c.987-3908G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 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=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.528 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173598.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KSR2	NM_173598.6	MANE Select	c.987-3908G>A		intron	N/A	NP_775869.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KSR2	ENST00000339824.7	TSL:5 MANE Select	c.987-3908G>A		intron	N/A	ENSP00000339952.4	Q6VAB6-1
	KSR2	ENST00000545002.1	TSL:2	n.132+2717G>A		intron	N/A

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

African (AFR) AF: 0.113 AC: 4709 AN: 41538

American (AMR) AF: 0.397 AC: 6058 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.553 AC: 1919 AN: 3472

East Asian (EAS) AF: 0.328 AC: 1697 AN: 5168

South Asian (SAS) AF: 0.477 AC: 2298 AN: 4822

European-Finnish (FIN) AF: 0.453 AC: 4799 AN: 10598

Middle Eastern (MID) AF: 0.544 AC: 160 AN: 294

European-Non Finnish (NFE) AF: 0.532 AC: 36183 AN: 67982

Other (OTH) AF: 0.432 AC: 914 AN: 2116

Alfa AF: 0.475 Hom.: 53222

Bravo AF: 0.366

Asia WGS AF: 0.394 AC: 1371 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.098
DANN	Benign	0.42
PhyloP100		-1.5
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: rs481745; hg19: chr12-118109371;