17-27549370-G-A

Variant names:

• chr17-27549370-G-A
• rs11656620
• NM_001394583.1:c.232-1198G>A

Variant summary

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

The NM_001394583.1(KSR1):​c.232-1198G>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
• Publications: 6 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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.276 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.232-1198G>A		intron	N/A	NP_001381512.1	A0A2R8Y5H9
	KSR1	NM_001367810.1		c.232-1198G>A		intron	N/A	NP_001354739.1
	KSR1	NM_014238.2		c.-180-1198G>A		intron	N/A	NP_055053.1	Q8IVT5-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KSR1	ENST00000644974.2	MANE Select	c.232-1198G>A		intron	N/A	ENSP00000494552.1	A0A2R8Y5H9
	KSR1	ENST00000398988.7	TSL:5	c.-180-1198G>A		intron	N/A	ENSP00000381958.3	Q8IVT5-4
	KSR1	ENST00000583370.5	TSL:3	c.-322-1198G>A		intron	N/A	ENSP00000464081.1	J3QR75

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

African (AFR) AF: 0.199 AC: 8253 AN: 41476

American (AMR) AF: 0.211 AC: 3232 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.342 AC: 1187 AN: 3472

East Asian (EAS) AF: 0.0334 AC: 173 AN: 5176

South Asian (SAS) AF: 0.135 AC: 649 AN: 4824

European-Finnish (FIN) AF: 0.227 AC: 2402 AN: 10584

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.279 AC: 18960 AN: 67972

Other (OTH) AF: 0.236 AC: 496 AN: 2106

Alfa AF: 0.259 Hom.: 6459

Bravo AF: 0.231

Asia WGS AF: 0.0840 AC: 291 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.27
DANN	Benign	0.67
PhyloP100		-1.6
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: rs11656620; hg19: chr17-25876396;