NM_004514.4:c.228C>T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_004514.4(FOXK2):​c.228C>T​(p.Ser76Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000314 in 1,526,872 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0012 (1 hom., cov: 30)
  • Exomes 𝑓: 0.00023 (1 hom.)
• Consequence: FOXK2 NM_004514.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.02).
• BP6: Variant 17-82520116-C-T is Benign according to our data. Variant chr17-82520116-C-T is described in ClinVar as [Benign]. Clinvar id is 711696.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.44 with no splicing effect.
• BS2: High AC in GnomAd4 at 161 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXK2	NM_004514.4	c.228C>T	p.Ser76Ser	synonymous_variant	Exon 1 of 9	ENST00000335255.10	NP_004505.2
FOXK2	XM_047435919.1	c.228C>T	p.Ser76Ser	synonymous_variant	Exon 1 of 9		XP_047291875.1
FOXK2	XM_047435920.1	c.228C>T	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>T	p.Ser76Ser	synonymous_variant	Exon 1 of 9	1	NM_004514.4	ENSP00000335677.5
FOXK2	ENST00000473637.6	n.228C>T		non_coding_transcript_exon_variant	Exon 1 of 10	1		ENSP00000436108.2
FOXK2	ENST00000527313.6	n.140C>T		non_coding_transcript_exon_variant	Exon 1 of 3	3
FOXK2	ENST00000570585.1	n.-178C>T		upstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.00116 AC: 161 AN: 138980 Hom.: 1 Cov.: 30

Gnomad AFR AF: 0.00386

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000221

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00254

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00162

GnomAD2 exomes AF: 0.000524 AC: 100 AN: 190992 AF XY: 0.000521

Gnomad AFR exome AF: 0.00472

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000115

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000229 AC: 318 AN: 1387784 Hom.: 1 Cov.: 33 AF XY: 0.000272 AC XY: 188 AN XY: 690540

African (AFR) AF: 0.00368 AC: 105 AN: 28516

American (AMR) AF: 0.000109 AC: 4 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: 0.00217 AC: 172 AN: 79282

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

Middle Eastern (MID) AF: 0.000244 AC: 1 AN: 4092

European-Non Finnish (NFE) AF: 0.0000121 AC: 13 AN: 1077080

Other (OTH) AF: 0.000406 AC: 23 AN: 56644

GnomAD4 genome AF: 0.00116 AC: 161 AN: 139088 Hom.: 1 Cov.: 30 AF XY: 0.00104 AC XY: 70 AN XY: 67588

African (AFR) AF: 0.00384 AC: 144 AN: 37456

American (AMR) AF: 0.000221 AC: 3 AN: 13592

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3258

East Asian (EAS) AF: 0.00 AC: 0 AN: 4642

South Asian (SAS) AF: 0.00255 AC: 11 AN: 4316

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9552

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 63310

Other (OTH) AF: 0.00160 AC: 3 AN: 1872

Alfa AF: 0.000298 Hom.: 0

Bravo AF: 0.00122

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 18, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	9.8
DANN	Benign	0.97
PhyloP100		0.44
PromoterAI		0.011	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
Mutation Taster		=100/0	polymorphism

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: COSV104646665; COSMIC: COSV104646665;