chr17-27495638-G-C

Variant names:

• chr17-27495638-G-C
• rs9332455
• NM_001394583.1:c.231+38764G>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.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
• Publications: 5 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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
KSR1	NM_001394583.1	c.231+38764G>C		intron_variant	Intron 1 of 20	ENST00000644974.2	NP_001381512.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KSR1	ENST00000644974.2	c.231+38764G>C		intron_variant	Intron 1 of 20		NM_001394583.1	ENSP00000494552.1
KSR1	ENST00000398988.7	c.-181+11787G>C		intron_variant	Intron 2 of 21	5		ENSP00000381958.3
KSR1	ENST00000583370.5	c.-323+11804G>C		intron_variant	Intron 2 of 5	3		ENSP00000464081.1
KSR1	ENST00000582311.1	n.262+11787G>C		intron_variant	Intron 2 of 3	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

African (AFR) AF: 0.509 AC: 21084 AN: 41462

American (AMR) AF: 0.442 AC: 6753 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.293 AC: 1016 AN: 3468

East Asian (EAS) AF: 0.312 AC: 1616 AN: 5174

South Asian (SAS) AF: 0.501 AC: 2418 AN: 4826

European-Finnish (FIN) AF: 0.376 AC: 3967 AN: 10556

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.331 AC: 22475 AN: 67994

Other (OTH) AF: 0.373 AC: 787 AN: 2112

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
PhyloP100		1.4
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: rs9332455; hg19: chr17-25822664;