rs1969543882

Variant names:

• chr16-86510568-C-A
• rs1969543882
• NM_001451.3:c.-2C>A

Your query was ambiguous. Multiple possible variants found:

• chr16-86510568-C-A
• chr16-86510568-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001451.3(FOXF1):​c.-2C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000829 in 1,206,166 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 8.3e-7 (0 hom.)
• Consequence: FOXF1 NM_001451.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.94
• Publications: 0 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: Orphanet, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001451.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXF1	NM_001451.3	MANE Select	c.-2C>A		5_prime_UTR	Exon 1 of 2	NP_001442.2	Q12946

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXF1	ENST00000262426.6	TSL:1 MANE Select	c.-2C>A		5_prime_UTR	Exon 1 of 2	ENSP00000262426.4	Q12946

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.29e-7 AC: 1 AN: 1206166 Hom.: 0 Cov.: 33 AF XY: 0.00000170 AC XY: 1 AN XY: 589932

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

African (AFR) AF: 0.0000422 AC: 1 AN: 23672

American (AMR) AF: 0.00 AC: 0 AN: 13716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18084

East Asian (EAS) AF: 0.00 AC: 0 AN: 26706

South Asian (SAS) AF: 0.00 AC: 0 AN: 48600

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29880

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3564

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 992992

Other (OTH) AF: 0.00 AC: 0 AN: 48952

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	21
DANN	Benign	0.95
PhyloP100		2.9
PromoterAI		0.038	Neutral

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: rs1969543882; hg19: chr16-86544174;