rs11656620

chr17-27549370-G-Achr17-27549370-G-C

Variant summary

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

The NM_001394583.1(KSR1):c.232-1198G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 152,112 control chromosomes in the GnomAD database, including 4,392 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 0.23 (4392 hom., cov: 32)
• Consequence: KSR1 NM_001394583.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.56

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KSR1	NM_001394583.1	c.232-1198G>A		intron_variant		ENST00000644974.2
LOC124903960	XR_007065680.1	n.201+2517C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KSR1	ENST00000644974.2	c.232-1198G>A		intron_variant			NM_001394583.1	P1
KSR1	ENST00000398988.7	c.-180-1198G>A		intron_variant		5
KSR1	ENST00000583370.5	c.-322-1198G>A		intron_variant		3
KSR1	ENST00000582311.1	n.263-1198G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.235 AC: 35660 AN: 151996 Hom.: 4395 Cov.: 32

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.234

Gnomad AMR AF: 0.212

Gnomad ASJ AF: 0.342

Gnomad EAS AF: 0.0335

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.227

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.279

Gnomad OTH AF: 0.239

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

GnomAD4 genome AF: 0.234 AC: 35665 AN: 152112 Hom.: 4392 Cov.: 32 AF XY: 0.229 AC XY: 17046 AN XY: 74372

Gnomad4 AFR AF: 0.199

Gnomad4 AMR AF: 0.211

Gnomad4 ASJ AF: 0.342

Gnomad4 EAS AF: 0.0334

Gnomad4 SAS AF: 0.135

Gnomad4 FIN AF: 0.227

Gnomad4 NFE AF: 0.279

Gnomad4 OTH AF: 0.236

Alfa AF: 0.172 Hom.: 406

Bravo AF: 0.231

Asia WGS AF: 0.0840 AC: 291 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	0.27
Dann	Benign	0.67

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: rs11656620; hg19: chr17-25876396;