16-86510566-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The NM_001451.3(FOXF1):c.-4C>T variant causes a 5 prime UTR change. The variant allele was found at a frequency of 0.000571 in 1,356,854 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00053 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00058 (0 hom.)
• Consequence: FOXF1 NM_001451.3 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.15

Genes affected

FOXF1 (HGNC:3809): (forkhead box F1) This gene belongs to the forkhead family of transcription factors which is characterized by a distinct forkhead domain. The specific function of this gene has not yet been determined; however, it may play a role in the regulation of pulmonary genes as well as embryonic development. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.25).
• BP6: Variant 16-86510566-C-T is Benign according to our data. Variant chr16-86510566-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3050972.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 80 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FOXF1	NM_001451.3	c.-4C>T		5_prime_UTR_variant	1/2	ENST00000262426.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FOXF1	ENST00000262426.6	c.-4C>T		5_prime_UTR_variant	1/2	1	NM_001451.3	P1

Frequencies

GnomAD3 genomes AF: 0.000528 AC: 80 AN: 151596 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000968

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000656

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00504

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000324

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000311 AC: 12 AN: 38554 Hom.: 0 AF XY: 0.000212 AC XY: 5 AN XY: 23584

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000211

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00169

Gnomad NFE exome AF: 0.000186

Gnomad OTH exome AF: 0.000963

GnomAD4 exome AF: 0.000577 AC: 695 AN: 1205150 Hom.: 0 Cov.: 33 AF XY: 0.000545 AC XY: 321 AN XY: 589304

Gnomad4 AFR exome AF: 0.0000423

Gnomad4 AMR exome AF: 0.000363

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00414

Gnomad4 NFE exome AF: 0.000554

Gnomad4 OTH exome AF: 0.000327

GnomAD4 genome AF: 0.000527 AC: 80 AN: 151704 Hom.: 0 Cov.: 32 AF XY: 0.000715 AC XY: 53 AN XY: 74168

Gnomad4 AFR AF: 0.0000966

Gnomad4 AMR AF: 0.0000655

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00504

Gnomad4 NFE AF: 0.000324

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000318 Hom.: 0

Bravo AF: 0.000249

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

FOXF1-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 25, 2020

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.25
Cadd	Benign	21
Dann	Uncertain	0.98

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: rs752749806; hg19: chr16-86544172;