16-86513281-T-C

Variant names:

• chr16-86513281-T-C
• rs7185244
• NM_001451.3:c.*196T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001451.3(FOXF1):​c.*196T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.807 in 598,490 control chromosomes in the GnomAD database, including 195,410 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.82 (51677 hom., cov: 33)
  • Exomes 𝑓: 0.80 (143733 hom.)
• Consequence: FOXF1 NM_001451.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.796
• Publications: 12 publications found

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]

FOXF1 Gene-Disease associations (from GenCC):

• alveolar capillary dysplasia with misalignment of pulmonary veins

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 16-86513281-T-C is Benign according to our data. Variant chr16-86513281-T-C is described in ClinVar as Benign. ClinVar VariationId is 1269725.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.882 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXF1	NM_001451.3	c.*196T>C		3_prime_UTR_variant	Exon 2 of 2	ENST00000262426.6	NP_001442.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXF1	ENST00000262426.6	c.*196T>C		3_prime_UTR_variant	Exon 2 of 2	1	NM_001451.3	ENSP00000262426.4

Frequencies

GnomAD3 genomes AF: 0.823 AC: 125141 AN: 152090 Hom.: 51617 Cov.: 33

Gnomad AFR AF: 0.889

Gnomad AMI AF: 0.714

Gnomad AMR AF: 0.857

Gnomad ASJ AF: 0.812

Gnomad EAS AF: 0.877

Gnomad SAS AF: 0.823

Gnomad FIN AF: 0.806

Gnomad MID AF: 0.820

Gnomad NFE AF: 0.775

Gnomad OTH AF: 0.824

GnomAD4 exome AF: 0.801 AC: 357477 AN: 446282 Hom.: 143733 Cov.: 4 AF XY: 0.801 AC XY: 188943 AN XY: 235798

African (AFR) AF: 0.884 AC: 10879 AN: 12312

American (AMR) AF: 0.883 AC: 16974 AN: 19232

Ashkenazi Jewish (ASJ) AF: 0.821 AC: 11134 AN: 13568

East Asian (EAS) AF: 0.908 AC: 27595 AN: 30398

South Asian (SAS) AF: 0.816 AC: 37451 AN: 45910

European-Finnish (FIN) AF: 0.807 AC: 22875 AN: 28344

Middle Eastern (MID) AF: 0.803 AC: 1549 AN: 1930

European-Non Finnish (NFE) AF: 0.775 AC: 208531 AN: 268912

Other (OTH) AF: 0.798 AC: 20489 AN: 25676

GnomAD4 genome AF: 0.823 AC: 125259 AN: 152208 Hom.: 51677 Cov.: 33 AF XY: 0.825 AC XY: 61357 AN XY: 74404

African (AFR) AF: 0.890 AC: 36953 AN: 41542

American (AMR) AF: 0.857 AC: 13116 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.812 AC: 2818 AN: 3472

East Asian (EAS) AF: 0.877 AC: 4532 AN: 5168

South Asian (SAS) AF: 0.823 AC: 3971 AN: 4826

European-Finnish (FIN) AF: 0.806 AC: 8536 AN: 10592

Middle Eastern (MID) AF: 0.813 AC: 239 AN: 294

European-Non Finnish (NFE) AF: 0.775 AC: 52698 AN: 67990

Other (OTH) AF: 0.826 AC: 1745 AN: 2112

Alfa AF: 0.797 Hom.: 62747

Bravo AF: 0.831

Asia WGS AF: 0.844 AC: 2933 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Sep 04, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	9.5
DANN	Benign	0.68
PhyloP100		0.80
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: rs7185244; hg19: chr16-86546887;