rs9791644

chr7-4683903-G-Achr7-4683903-G-C

Variant summary

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

The NM_001037165.2(FOXK1):c.560+1035G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 152,190 control chromosomes in the GnomAD database, including 1,370 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 0.13 (1370 hom., cov: 32)
• Consequence: FOXK1 NM_001037165.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.385

Genes affected

FOXK1 (HGNC:23480): (forkhead box K1) Enables 14-3-3 protein binding activity; DNA-binding transcription repressor activity, RNA polymerase II-specific; and transcription cis-regulatory region binding activity. Involved in several processes, including cellular glucose homeostasis; negative regulation of autophagy; and regulation of transcription, DNA-templated. Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FOXK1	NM_001037165.2	c.560+1035G>A		intron_variant		ENST00000328914.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FOXK1	ENST00000328914.5	c.560+1035G>A		intron_variant		2	NM_001037165.2	P1

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19240 AN: 152072 Hom.: 1368 Cov.: 32

Gnomad AFR AF: 0.0777

Gnomad AMI AF: 0.0363

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.0816

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.0790

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.132

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

GnomAD4 genome AF: 0.126 AC: 19248 AN: 152190 Hom.: 1370 Cov.: 32 AF XY: 0.123 AC XY: 9146 AN XY: 74394

Gnomad4 AFR AF: 0.0779

Gnomad4 AMR AF: 0.110

Gnomad4 ASJ AF: 0.112

Gnomad4 EAS AF: 0.0814

Gnomad4 SAS AF: 0.151

Gnomad4 FIN AF: 0.0790

Gnomad4 NFE AF: 0.171

Gnomad4 OTH AF: 0.131

Alfa AF: 0.162 Hom.: 2661

Bravo AF: 0.124

Asia WGS AF: 0.107 AC: 374 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	4.2
Dann	Benign	0.68
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

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: rs9791644; hg19: chr7-4723534;