Genetic Variant NM_001394583.1: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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KSR1	NM_001394583.1 link	c.2709-120G>A		intron_variant	Intron 20 of 20	ENST00000644974.2	NP_001381512.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KSR1	ENST00000644974.2 link	c.2709-120G>A		intron_variant	Intron 20 of 20		NM_001394583.1	ENSP00000494552.1
ENSG00000266728	ENST00000584605.5 link	n.-170G>A		upstream_gene_variant		2		ENSP00000463557.1

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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over