chr7-4728407-T-C

Position:

• chr7-4728407-T-C

Variant summary

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

The NM_001037165.2(FOXK1):​c.561-12431T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0814 in 152,264 control chromosomes in the GnomAD database, including 631 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 0.081 (631 hom., cov: 32)
• Consequence: FOXK1 NM_001037165.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.138 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOXK1	NM_001037165.2	c.561-12431T>C		intron_variant		ENST00000328914.5	NP_001032242.1
LOC124901581	XR_007060199.1	n.5130T>C		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOXK1	ENST00000328914.5	c.561-12431T>C		intron_variant		2	NM_001037165.2	ENSP00000328720	P1
	ENST00000658333.1	n.2175T>C		non_coding_transcript_exon_variant	2/2

Frequencies

GnomAD3 genomes AF: 0.0812 AC: 12353 AN: 152146 Hom.: 623 Cov.: 32

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.0570

Gnomad AMR AF: 0.0717

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0345

Gnomad FIN AF: 0.0378

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0615

Gnomad OTH AF: 0.0942

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

GnomAD4 genome AF: 0.0814 AC: 12393 AN: 152264 Hom.: 631 Cov.: 32 AF XY: 0.0791 AC XY: 5889 AN XY: 74458

Gnomad4 AFR AF: 0.141

Gnomad4 AMR AF: 0.0715

Gnomad4 ASJ AF: 0.114

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0346

Gnomad4 FIN AF: 0.0378

Gnomad4 NFE AF: 0.0615

Gnomad4 OTH AF: 0.0918

Alfa AF: 0.0656 Hom.: 499

Bravo AF: 0.0895

Asia WGS AF: 0.0260 AC: 91 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.50
DANN	Benign	0.39

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: rs7788807; hg19: chr7-4768038;