dbSNP rs2241906: KSR1:c.2709-165C>T (chr17-27623149-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001394583.1(KSR1):c.2709-165C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 647,430 control chromosomes in the GnomAD database, including 16,735 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 0.20 ( 3333 hom., cov: 33)

Exomes 𝑓: 0.23 ( 13402 hom. )

Consequence

KSR1
NM_001394583.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.672

Publications

15 publications found

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:

ENSG00000266728 (HGNC:):

ENSG00000266728 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.27 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394583.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
KSR1	NM_001394583.1	MANE Select	c.2709-165C>T	intron	N/A	NP_001381512.1
KSR1	NM_014238.2		c.*1214C>T	3_prime_UTR	Exon 22 of 22	NP_055053.1
KSR1	NM_001367810.1		c.2628-165C>T	intron	N/A	NP_001354739.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
KSR1	ENST00000644974.2	MANE Select	c.2709-165C>T	intron	N/A	ENSP00000494552.1
KSR1	ENST00000398988.7	TSL:5	c.*1214C>T	3_prime_UTR	Exon 22 of 22	ENSP00000381958.3
KSR1	ENST00000582410.5	TSL:2	c.*1214C>T	3_prime_UTR	Exon 4 of 4	ENSP00000464680.1

Frequencies

GnomAD3 genomes

AF:

0.203

AC:

30881

AN:

151940

Hom.:

3332

Cov.:

show subpopulations

Gnomad AFR

AF:

0.136

Gnomad AMI

AF:

0.121

Gnomad AMR

AF:

0.277

Gnomad ASJ

AF:

0.256

Gnomad EAS

AF:

0.245

Gnomad SAS

AF:

0.237

Gnomad FIN

AF:

0.192

Gnomad MID

AF:

0.155

Gnomad NFE

AF:

0.222

Gnomad OTH

AF:

0.230

GnomAD4 exome

AF:

0.229

AC:

113500

AN:

495372

Hom.:

13402

Cov.:

AF XY:

0.228

AC XY:

60716

AN XY:

265736

show subpopulations

African (AFR)

AF:

0.138

AC:

1911

AN:

13874

American (AMR)

AF:

0.306

AC:

8151

AN:

26600

Ashkenazi Jewish (ASJ)

AF:

0.272

AC:

4429

AN:

16298

East Asian (EAS)

AF:

0.277

AC:

8792

AN:

31726

South Asian (SAS)

AF:

0.237

AC:

12155

AN:

51314

European-Finnish (FIN)

AF:

0.189

AC:

5918

AN:

31294

Middle Eastern (MID)

AF:

0.199

AC:

503

AN:

2530

European-Non Finnish (NFE)

AF:

0.223

AC:

65402

AN:

293542

Other (OTH)

AF:

0.221

AC:

6239

AN:

28194

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

4587

9173

13760

18346

22933

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

422

844

1266

1688

2110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.203

AC:

30884

AN:

152058

Hom.:

3333

Cov.:

AF XY:

0.202

AC XY:

14978

AN XY:

74326

show subpopulations

African (AFR)

AF:

0.136

AC:

5633

AN:

41478

American (AMR)

AF:

0.277

AC:

4236

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.256

AC:

889

AN:

3468

East Asian (EAS)

AF:

0.244

AC:

1262

AN:

5168

South Asian (SAS)

AF:

0.236

AC:

1136

AN:

4806

European-Finnish (FIN)

AF:

0.192

AC:

2035

AN:

10580

Middle Eastern (MID)

AF:

0.153

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.222

AC:

15060

AN:

67956

Other (OTH)

AF:

0.227

AC:

478

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1252

2504

3757

5009

6261

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

340

680

1020

1360

1700

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.219

Hom.:

2314

Bravo

AF:

0.208

Asia WGS

AF:

0.222

AC:

771

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

6.6

(source)

DANN

Benign

0.48

PhyloP100

0.67

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over