16-86511850-C-T

Variant names:

• chr16-86511850-C-T
• rs2078304
• NM_001451.3:c.979+302C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001451.3(FOXF1):​c.979+302C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0466 in 152,132 control chromosomes in the GnomAD database, including 274 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.047 (274 hom., cov: 34)
• Consequence: FOXF1 NM_001451.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.355
• Publications: 2 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 16-86511850-C-T is Benign according to our data. Variant chr16-86511850-C-T is described in ClinVar as Benign. ClinVar VariationId is 1252327.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0883 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXF1	NM_001451.3	c.979+302C>T		intron_variant	Intron 1 of 1	ENST00000262426.6	NP_001442.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXF1	ENST00000262426.6	c.979+302C>T		intron_variant	Intron 1 of 1	1	NM_001451.3	ENSP00000262426.4

Frequencies

GnomAD3 genomes AF: 0.0465 AC: 7073 AN: 152014 Hom.: 273 Cov.: 34

Gnomad AFR AF: 0.0905

Gnomad AMI AF: 0.00220

Gnomad AMR AF: 0.0219

Gnomad ASJ AF: 0.0300

Gnomad EAS AF: 0.0124

Gnomad SAS AF: 0.0255

Gnomad FIN AF: 0.0791

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0260

Gnomad OTH AF: 0.0401

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0466 AC: 7088 AN: 152132 Hom.: 274 Cov.: 34 AF XY: 0.0491 AC XY: 3653 AN XY: 74364

African (AFR) AF: 0.0907 AC: 3767 AN: 41514

American (AMR) AF: 0.0218 AC: 334 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0300 AC: 104 AN: 3470

East Asian (EAS) AF: 0.0124 AC: 64 AN: 5148

South Asian (SAS) AF: 0.0249 AC: 120 AN: 4826

European-Finnish (FIN) AF: 0.0791 AC: 837 AN: 10586

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0260 AC: 1767 AN: 67968

Other (OTH) AF: 0.0397 AC: 84 AN: 2116

Alfa AF: 0.0263 Hom.: 797

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 12, 2019

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	-0.76
CADD	Benign	2.6
DANN	Benign	0.65
PhyloP100		-0.35
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: rs2078304; hg19: chr16-86545456;