rs148930372

Variant names:

• chr17-82520116-C-A
• rs148930372
• NM_004514.4:c.228C>A

Your query was ambiguous. Multiple possible variants found:

• chr17-82520116-C-A
• chr17-82520116-C-T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 0P and 3B. BP4_Moderate BP7

The NM_004514.4(FOXK2):​c.228C>A​(p.Ser76Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S76S) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.00031 (0 hom., cov: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FOXK2 NM_004514.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.440
• Publications: 0 publications found

Genes affected

FOXK2 (HGNC:6036): (forkhead box K2) The protein encoded by this gene contains a fork head DNA binding domain. This protein can bind to the purine-rich motifs of the HIV long terminal repeat (LTR), and to the similar purine-rich motif in the interleukin 2 (IL2) promoter. It may be involved in the regulation of viral and cellular promoter elements. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.051).
• BP7: Synonymous conserved (PhyloP=0.44 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXK2	NM_004514.4	c.228C>A	p.Ser76Ser	synonymous_variant	Exon 1 of 9	ENST00000335255.10	NP_004505.2
FOXK2	XM_047435919.1	c.228C>A	p.Ser76Ser	synonymous_variant	Exon 1 of 9		XP_047291875.1
FOXK2	XM_047435920.1	c.228C>A	p.Ser76Ser	synonymous_variant	Exon 1 of 5		XP_047291876.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXK2	ENST00000335255.10	c.228C>A	p.Ser76Ser	synonymous_variant	Exon 1 of 9	1	NM_004514.4	ENSP00000335677.5
FOXK2	ENST00000473637.6	n.228C>A		non_coding_transcript_exon_variant	Exon 1 of 10	1		ENSP00000436108.2
FOXK2	ENST00000527313.6	n.140C>A		non_coding_transcript_exon_variant	Exon 1 of 3	3
FOXK2	ENST00000570585.1	n.-178C>A		upstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.000307 AC: 42 AN: 136966 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.000628

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000299

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000217

Gnomad SAS AF: 0.000700

Gnomad FIN AF: 0.000105

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000144

Gnomad OTH AF: 0.000549

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1387786 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 690542

African (AFR) AF: 0.00 AC: 0 AN: 28516

American (AMR) AF: 0.00 AC: 0 AN: 36558

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24054

East Asian (EAS) AF: 0.00 AC: 0 AN: 32010

South Asian (SAS) AF: 0.00 AC: 0 AN: 79286

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49548

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4092

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1077078

Other (OTH) AF: 0.00 AC: 0 AN: 56644

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000306 AC: 42 AN: 137070 Hom.: 0 Cov.: 30 AF XY: 0.000285 AC XY: 19 AN XY: 66686

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000626 AC: 23 AN: 36764

American (AMR) AF: 0.000299 AC: 4 AN: 13394

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3184

East Asian (EAS) AF: 0.000218 AC: 1 AN: 4596

South Asian (SAS) AF: 0.000701 AC: 3 AN: 4278

European-Finnish (FIN) AF: 0.000105 AC: 1 AN: 9514

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 256

European-Non Finnish (NFE) AF: 0.000144 AC: 9 AN: 62414

Other (OTH) AF: 0.000544 AC: 1 AN: 1838

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	9.3
DANN	Benign	0.92
PhyloP100		0.44
PromoterAI		-0.014	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1

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: rs148930372; hg19: chr17-80477992; COSMIC: COSV100081943; COSMIC: COSV100081943;