rs2948527

Variant names:

• chr17-27545159-T-C
• rs2948527
• NM_001394583.1:c.232-5409T>C

Variant summary

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

The NM_001394583.1(KSR1):​c.232-5409T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.409 in 151,986 control chromosomes in the GnomAD database, including 13,368 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 0.41 (13368 hom., cov: 32)
• Consequence: KSR1 NM_001394583.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0150
• Publications: 2 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]

LOC124903960 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.53 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KSR1	NM_001394583.1	MANE Select	c.232-5409T>C		intron	N/A	NP_001381512.1
	KSR1	NM_001367810.1		c.232-5409T>C		intron	N/A	NP_001354739.1
	KSR1	NM_014238.2		c.-180-5409T>C		intron	N/A	NP_055053.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KSR1	ENST00000644974.2	MANE Select	c.232-5409T>C		intron	N/A	ENSP00000494552.1
	KSR1	ENST00000398988.7	TSL:5	c.-180-5409T>C		intron	N/A	ENSP00000381958.3
	KSR1	ENST00000583370.5	TSL:3	c.-322-5409T>C		intron	N/A	ENSP00000464081.1

Frequencies

GnomAD3 genomes AF: 0.409 AC: 62088 AN: 151866 Hom.: 13348 Cov.: 32

Gnomad AFR AF: 0.536

Gnomad AMI AF: 0.401

Gnomad AMR AF: 0.452

Gnomad ASJ AF: 0.281

Gnomad EAS AF: 0.316

Gnomad SAS AF: 0.487

Gnomad FIN AF: 0.374

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.336

Gnomad OTH AF: 0.385

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

GnomAD4 genome AF: 0.409 AC: 62157 AN: 151986 Hom.: 13368 Cov.: 32 AF XY: 0.412 AC XY: 30591 AN XY: 74282

African (AFR) AF: 0.536 AC: 22210 AN: 41422

American (AMR) AF: 0.452 AC: 6899 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.281 AC: 975 AN: 3470

East Asian (EAS) AF: 0.316 AC: 1631 AN: 5158

South Asian (SAS) AF: 0.486 AC: 2343 AN: 4818

European-Finnish (FIN) AF: 0.374 AC: 3959 AN: 10576

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.336 AC: 22858 AN: 67960

Other (OTH) AF: 0.385 AC: 814 AN: 2112

Alfa AF: 0.360 Hom.: 16997

Bravo AF: 0.421

Asia WGS AF: 0.429 AC: 1491 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.0
DANN	Benign	0.64
PhyloP100		-0.015
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: rs2948527; hg19: chr17-25872185;