chr17-27516617-G-A

Variant names:

• chr17-27516617-G-A
• rs2945412
• NM_001394583.1:c.232-33951G>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.232-33951G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.641 in 151,904 control chromosomes in the GnomAD database, including 31,837 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 0.64 (31837 hom., cov: 31)
• Consequence: KSR1 NM_001394583.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.769
• Publications: 47 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.764 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KSR1	NM_001394583.1	c.232-33951G>A		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.232-33951G>A		intron_variant	Intron 1 of 20		NM_001394583.1	ENSP00000494552.1
KSR1	ENST00000398988.7	c.-181+32766G>A		intron_variant	Intron 2 of 21	5		ENSP00000381958.3
KSR1	ENST00000583370.5	c.-323+32783G>A		intron_variant	Intron 2 of 5	3		ENSP00000464081.1
KSR1	ENST00000582311.1	n.262+32766G>A		intron_variant	Intron 2 of 3	2

Frequencies

GnomAD3 genomes AF: 0.641 AC: 97273 AN: 151788 Hom.: 31813 Cov.: 31

Gnomad AFR AF: 0.771

Gnomad AMI AF: 0.631

Gnomad AMR AF: 0.622

Gnomad ASJ AF: 0.591

Gnomad EAS AF: 0.343

Gnomad SAS AF: 0.638

Gnomad FIN AF: 0.658

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.589

Gnomad OTH AF: 0.632

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

GnomAD4 genome AF: 0.641 AC: 97341 AN: 151904 Hom.: 31837 Cov.: 31 AF XY: 0.641 AC XY: 47560 AN XY: 74196

African (AFR) AF: 0.771 AC: 31927 AN: 41430

American (AMR) AF: 0.622 AC: 9491 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.591 AC: 2050 AN: 3468

East Asian (EAS) AF: 0.343 AC: 1766 AN: 5152

South Asian (SAS) AF: 0.638 AC: 3070 AN: 4812

European-Finnish (FIN) AF: 0.658 AC: 6913 AN: 10514

Middle Eastern (MID) AF: 0.592 AC: 174 AN: 294

European-Non Finnish (NFE) AF: 0.589 AC: 40052 AN: 67956

Other (OTH) AF: 0.629 AC: 1324 AN: 2104

Alfa AF: 0.605 Hom.: 66714

Bravo AF: 0.645

Asia WGS AF: 0.522 AC: 1815 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	2.5
DANN	Benign	0.31
PhyloP100		0.77
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: rs2945412; hg19: chr17-25843643;