Variant rs2293180 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001394583.1(KSR1):c.665C>T(p.Ala222Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 1,613,452 control chromosomes in the GnomAD database, including 15,654 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/16 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.14 ( 1624 hom., cov: 32)

Exomes 𝑓: 0.13 ( 14030 hom. )

Consequence

KSR1
NM_001394583.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.584

Variant links:

Genes affected

KSR1 (HGNC:6465): (kinase suppressor of ras 1) Enables 14-3-3 protein binding activity; ATP binding activity; and protein C-terminus binding activity. Involved in positive regulation of MAPK cascade. Located in endoplasmic reticulum and membrane. Part of protein-containing complex. Implicated in breast adenocarcinoma. Biomarker of breast cancer. [provided by Alliance of Genome Resources, Apr 2022]

KSR1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005291939).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.224 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KSR1	NM_001394583.1 linkuse as main transcript	c.665C>T	p.Ala222Val	missense_variant	4/21	ENST00000644974.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KSR1	ENST00000644974.2 linkuse as main transcript	c.665C>T	p.Ala222Val	missense_variant	4/21		NM_001394583.1	P1

Frequencies

GnomAD3 genomes

AF:

0.138

AC:

21048

AN:

151986

Hom.:

1620

Cov.:

show subpopulations

Gnomad AFR

AF:

0.134

Gnomad AMI

AF:

0.0998

Gnomad AMR

AF:

0.230

Gnomad ASJ

AF:

0.188

Gnomad EAS

AF:

0.204

Gnomad SAS

AF:

0.195

Gnomad FIN

AF:

0.0943

Gnomad MID

AF:

0.101

Gnomad NFE

AF:

0.116

Gnomad OTH

AF:

0.155

GnomAD3 exomes

AF:

0.159

AC:

39262

AN:

247710

Hom.:

3593

AF XY:

0.156

AC XY:

20997

AN XY:

134628

show subpopulations

Gnomad AFR exome

AF:

0.134

Gnomad AMR exome

AF:

0.275

Gnomad ASJ exome

AF:

0.199

Gnomad EAS exome

AF:

0.214

Gnomad SAS exome

AF:

0.192

Gnomad FIN exome

AF:

0.0905

Gnomad NFE exome

AF:

0.118

Gnomad OTH exome

AF:

0.152

GnomAD4 exome

AF:

0.132

AC:

193082

AN:

1461348

Hom.:

14030

Cov.:

AF XY:

0.133

AC XY:

96985

AN XY:

727000

show subpopulations

Gnomad4 AFR exome

AF:

0.141

Gnomad4 AMR exome

AF:

0.273

Gnomad4 ASJ exome

AF:

0.200

Gnomad4 EAS exome

AF:

0.245

Gnomad4 SAS exome

AF:

0.190

Gnomad4 FIN exome

AF:

0.0924

Gnomad4 NFE exome

AF:

0.118

Gnomad4 OTH exome

AF:

0.137

GnomAD4 genome

AF:

0.138

AC:

21057

AN:

152104

Hom.:

1624

Cov.:

AF XY:

0.140

AC XY:

10380

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.134

Gnomad4 AMR

AF:

0.230

Gnomad4 ASJ

AF:

0.188

Gnomad4 EAS

AF:

0.203

Gnomad4 SAS

AF:

0.194

Gnomad4 FIN

AF:

0.0943

Gnomad4 NFE

AF:

0.116

Gnomad4 OTH

AF:

0.154

Alfa

AF:

0.130

Hom.:

2383

Bravo

AF:

0.151

TwinsUK

AF:

0.121

AC:

448

ALSPAC

AF:

0.117

AC:

450

ESP6500AA

AF:

0.129

AC:

541

ESP6500EA

AF:

0.118

AC:

990

ExAC

AF:

0.153

AC:

18484

Asia WGS

AF:

0.182

AC:

634

AN:

3478

EpiCase

AF:

0.123

EpiControl

AF:

0.118

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.29

.;T;.;.;.;.

Eigen

Benign

-0.80

Eigen_PC

Benign

-0.75

FATHMM_MKL

Benign

0.25

LIST_S2

Uncertain

0.86

D;D;D;D;.;D

MetaRNN

Benign

0.0053

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Benign

0.37

REVEL

Benign

0.051

Sift4G

Benign

0.53

.;T;T;T;T;.

Vest4

0.041

MPC

0.38

ClinPred

0.0017

GERP RS

1.2

gMVP

0.13

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over