17-27623194-G-A

Position:

• chr17-27623194-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.41

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
KSR1	NM_001394583.1	c.2709-120G>A		intron_variant		ENST00000644974.2	NP_001381512.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KSR1	ENST00000644974.2	c.2709-120G>A		intron_variant			NM_001394583.1	ENSP00000494552	P1

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

Gnomad4 AFR exome AF: 0.145

Gnomad4 AMR exome AF: 0.309

Gnomad4 ASJ exome AF: 0.272

Gnomad4 EAS exome AF: 0.277

Gnomad4 SAS exome AF: 0.238

Gnomad4 FIN exome AF: 0.190

Gnomad4 NFE exome AF: 0.223

Gnomad4 OTH exome AF: 0.221

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

Gnomad4 AFR AF: 0.141

Gnomad4 AMR AF: 0.279

Gnomad4 ASJ AF: 0.256

Gnomad4 EAS AF: 0.245

Gnomad4 SAS AF: 0.237

Gnomad4 FIN AF: 0.193

Gnomad4 NFE AF: 0.221

Gnomad4 OTH AF: 0.228

Alfa AF: 0.223 Hom.: 5298

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
DANN	Benign	0.50

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

Other links and lift over

dbSNP: rs1075952; hg19: chr17-25950220; COSMIC: COSV52041735; COSMIC: COSV52041735;