Genetic Variant KSR1:c.2709-120G>A (chr17-27623194-G-A) – 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.2709-120G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 696,586 control chromosomes in the GnomAD database, including 18,251 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 ( 3373 hom., cov: 32)

Exomes 𝑓: 0.23 ( 14878 hom. )

Consequence

KSR1
NM_001394583.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.41

Publications

21 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=-0.9).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.272 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.2709-120G>A	intron	N/A	NP_001381512.1
KSR1	NM_014238.2		c.*1259G>A	3_prime_UTR	Exon 22 of 22	NP_055053.1
KSR1	NM_001367810.1		c.2628-120G>A	intron	N/A	NP_001354739.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
KSR1	ENST00000644974.2	MANE Select	c.2709-120G>A	intron	N/A	ENSP00000494552.1
KSR1	ENST00000398988.7	TSL:5	c.*1259G>A	3_prime_UTR	Exon 22 of 22	ENSP00000381958.3
KSR1	ENST00000582410.5	TSL:2	c.*1259G>A	3_prime_UTR	Exon 4 of 4	ENSP00000464680.1

Frequencies

GnomAD3 genomes

AF:

0.205

AC:

31140

AN:

151996

Hom.:

3372

Cov.:

show subpopulations

Gnomad AFR

AF:

0.141

Gnomad AMI

AF:

0.121

Gnomad AMR

AF:

0.279

Gnomad ASJ

AF:

0.256

Gnomad EAS

AF:

0.245

Gnomad SAS

AF:

0.237

Gnomad FIN

AF:

0.193

Gnomad MID

AF:

0.155

Gnomad NFE

AF:

0.222

Gnomad OTH

AF:

0.231

GnomAD4 exome

AF:

0.230

AC:

125464

AN:

544472

Hom.:

14878

Cov.:

AF XY:

0.230

AC XY:

67689

AN XY:

294684

show subpopulations

African (AFR)

AF:

0.145

AC:

2249

AN:

15542

American (AMR)

AF:

0.309

AC:

10512

AN:

33988

Ashkenazi Jewish (ASJ)

AF:

0.272

AC:

5376

AN:

19744

East Asian (EAS)

AF:

0.277

AC:

8879

AN:

32082

South Asian (SAS)

AF:

0.238

AC:

14561

AN:

61078

European-Finnish (FIN)

AF:

0.190

AC:

6358

AN:

33524

Middle Eastern (MID)

AF:

0.191

AC:

725

AN:

3802

European-Non Finnish (NFE)

AF:

0.223

AC:

70087

AN:

314342

Other (OTH)

AF:

0.221

AC:

6717

AN:

30370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

5237

10474

15712

20949

26186

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

452

904

1356

1808

2260

<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:

0.205

AC:

31150

AN:

152114

Hom.:

3373

Cov.:

AF XY:

0.203

AC XY:

15107

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.141

AC:

5863

AN:

41506

American (AMR)

AF:

0.279

AC:

4263

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.256

AC:

890

AN:

3472

East Asian (EAS)

AF:

0.245

AC:

1269

AN:

5184

South Asian (SAS)

AF:

0.237

AC:

1137

AN:

4802

European-Finnish (FIN)

AF:

0.193

AC:

2037

AN:

10574

Middle Eastern (MID)

AF:

0.153

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.221

AC:

15056

AN:

67982

Other (OTH)

AF:

0.228

AC:

480

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1268

2536

3804

5072

6340

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

342

684

1026

1368

1710

<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:

0.218

Hom.:

7383

Bravo

AF:

0.210

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.014

(source)

DANN

Benign

0.50

PhyloP100

-2.4

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