rs9332455

chr17-27495638-G-Cchr17-27495638-G-T

Variant summary

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

The NM_001394583.1(KSR1):c.231+38764G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.398 in 152,080 control chromosomes in the GnomAD database, including 12,589 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 0.40 (12589 hom., cov: 32)
• Consequence: KSR1 NM_001394583.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.41

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=-0.73).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.503 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KSR1	NM_001394583.1	c.231+38764G>C		intron_variant		ENST00000644974.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KSR1	ENST00000644974.2	c.231+38764G>C		intron_variant			NM_001394583.1	P1
KSR1	ENST00000398988.7	c.-181+11787G>C		intron_variant		5
KSR1	ENST00000583370.5	c.-323+11804G>C		intron_variant		3
KSR1	ENST00000582311.1	n.262+11787G>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.398 AC: 60519 AN: 151962 Hom.: 12572 Cov.: 32

Gnomad AFR AF: 0.508

Gnomad AMI AF: 0.401

Gnomad AMR AF: 0.442

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.312

Gnomad SAS AF: 0.502

Gnomad FIN AF: 0.376

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.331

Gnomad OTH AF: 0.372

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.398 AC: 60579 AN: 152080 Hom.: 12589 Cov.: 32 AF XY: 0.402 AC XY: 29894 AN XY: 74320

Gnomad4 AFR AF: 0.509

Gnomad4 AMR AF: 0.442

Gnomad4 ASJ AF: 0.293

Gnomad4 EAS AF: 0.312

Gnomad4 SAS AF: 0.501

Gnomad4 FIN AF: 0.376

Gnomad4 NFE AF: 0.331

Gnomad4 OTH AF: 0.373

Alfa AF: 0.238 Hom.: 550

Bravo AF: 0.408

Asia WGS AF: 0.426 AC: 1479 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
Cadd	Benign	15
Dann	Benign	0.69

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: rs9332455; hg19: chr17-25822664;