17-27623194-G-A

Variant names:

• chr17-27623194-G-A
• rs1075952
• NM_001394583.1:c.2709-120G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014238.2(KSR1):​c.*1259G>A variant causes a 3 prime UTR 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_014238.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.41
• Publications: 21 publications found

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]

ENSG00000266728 (HGNC:):

ACMG classification

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_014238.2. 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
	KSR1	NM_001394583.1	MANE Select	c.2709-120G>A		intron	N/A	NP_001381512.1	A0A2R8Y5H9
	KSR1	NM_014238.2		c.*1259G>A		3_prime_UTR	Exon 22 of 22	NP_055053.1	Q8IVT5-4
	KSR1	NM_001367810.1		c.2628-120G>A		intron	N/A	NP_001354739.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KSR1	ENST00000644974.2	MANE Select	c.2709-120G>A		intron	N/A	ENSP00000494552.1	A0A2R8Y5H9
	KSR1	ENST00000398988.7	TSL:5	c.*1259G>A		3_prime_UTR	Exon 22 of 22	ENSP00000381958.3	Q8IVT5-4
	KSR1	ENST00000582410.5	TSL:2	c.*1259G>A		3_prime_UTR	Exon 4 of 4	ENSP00000464680.1	J3QSG8

Frequencies

GnomAD3 genomes AF: 0.205 AC: 31140 AN: 151996 Hom.: 3372 Cov.: 32

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.: 0 AF XY: 0.230 AC XY: 67689 AN XY: 294684

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

GnomAD4 genome AF: 0.205 AC: 31150 AN: 152114 Hom.: 3373 Cov.: 32 AF XY: 0.203 AC XY: 15107 AN XY: 74338

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: 45 AN: 294

European-Non Finnish (NFE) AF: 0.221 AC: 15056 AN: 67982

Other (OTH) AF: 0.228 AC: 480 AN: 2108

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
DANN	Benign	0.50
PhyloP100		-2.4
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: rs1075952; hg19: chr17-25950220; COSMIC: COSV52041735; COSMIC: COSV52041735;