rs2948529

Variant names:

• chr17-27543516-C-T
• rs2948529
• NM_001394583.1:c.232-7052C>T

Variant summary

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

The NM_001394583.1(KSR1):​c.232-7052C>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
• Publications: 0 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=-0.81).
• 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 rank	MANE	Protein	UniProt
KSR1	NM_001394583.1	c.232-7052C>T		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.232-7052C>T		intron_variant	Intron 1 of 20		NM_001394583.1	ENSP00000494552.1
KSR1	ENST00000398988.7	c.-180-7052C>T		intron_variant	Intron 2 of 21	5		ENSP00000381958.3
KSR1	ENST00000583370.5	c.-322-7052C>T		intron_variant	Intron 2 of 5	3		ENSP00000464081.1
KSR1	ENST00000582311.1	n.263-7052C>T		intron_variant	Intron 2 of 3	2

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

African (AFR) AF: 0.532 AC: 22063 AN: 41458

American (AMR) AF: 0.449 AC: 6860 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.280 AC: 972 AN: 3468

East Asian (EAS) AF: 0.315 AC: 1630 AN: 5170

South Asian (SAS) AF: 0.484 AC: 2328 AN: 4812

European-Finnish (FIN) AF: 0.373 AC: 3938 AN: 10562

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.336 AC: 22837 AN: 67954

Other (OTH) AF: 0.384 AC: 811 AN: 2110

Alfa AF: 0.386 Hom.: 1509

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
PhyloP100		-1.1
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: rs2948529; hg19: chr17-25870542;