NM_001037165.2:c.560+1035G>A

Variant names:

• chr7-4683903-G-A
• rs9791644
• NM_001037165.2:c.560+1035G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
FOXK1	NM_001037165.2	c.560+1035G>A		intron_variant	Intron 1 of 8	ENST00000328914.5	NP_001032242.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXK1	ENST00000328914.5	c.560+1035G>A		intron_variant	Intron 1 of 8	2	NM_001037165.2	ENSP00000328720.4

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

African (AFR) AF: 0.0779 AC: 3234 AN: 41540

American (AMR) AF: 0.110 AC: 1683 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.112 AC: 389 AN: 3472

East Asian (EAS) AF: 0.0814 AC: 420 AN: 5162

South Asian (SAS) AF: 0.151 AC: 729 AN: 4828

European-Finnish (FIN) AF: 0.0790 AC: 838 AN: 10614

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.171 AC: 11608 AN: 67974

Other (OTH) AF: 0.131 AC: 277 AN: 2108

Alfa AF: 0.156 Hom.: 3483

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
PhyloP100		-0.39
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
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: rs9791644; hg19: chr7-4723534;