rs2948529

Positions:

• chr17-27543516-C-T

Variant summary

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

The NM_001394583.1(KSR1):​c.232-7052C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.407 in 152,028 control chromosomes in the GnomAD database, including 13,247 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 (13247 hom., cov: 32)
• Consequence: KSR1 NM_001394583.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.526 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KSR1	NM_001394583.1	c.232-7052C>T		intron_variant		ENST00000644974.2	NP_001381512.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KSR1	ENST00000644974.2	c.232-7052C>T		intron_variant			NM_001394583.1	ENSP00000494552.1

Frequencies

GnomAD3 genomes AF: 0.407 AC: 61842 AN: 151910 Hom.: 13230 Cov.: 32

Gnomad AFR AF: 0.532

Gnomad AMI AF: 0.400

Gnomad AMR AF: 0.449

Gnomad ASJ AF: 0.280

Gnomad EAS AF: 0.315

Gnomad SAS AF: 0.484

Gnomad FIN AF: 0.373

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.336

Gnomad OTH AF: 0.384

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

GnomAD4 genome AF: 0.407 AC: 61908 AN: 152028 Hom.: 13247 Cov.: 32 AF XY: 0.410 AC XY: 30464 AN XY: 74306

Gnomad4 AFR AF: 0.532

Gnomad4 AMR AF: 0.449

Gnomad4 ASJ AF: 0.280

Gnomad4 EAS AF: 0.315

Gnomad4 SAS AF: 0.484

Gnomad4 FIN AF: 0.373

Gnomad4 NFE AF: 0.336

Gnomad4 OTH AF: 0.384

Alfa AF: 0.379 Hom.: 1396

Bravo AF: 0.418

Asia WGS AF: 0.424 AC: 1473 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.20
DANN	Benign	0.83

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: rs2948529; hg19: chr17-25870542;