rs78816814

Positions:

• chr16-86566986-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005251.3(FOXC2):​c.-350G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0436 in 151,724 control chromosomes in the GnomAD database, including 330 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.044 (330 hom., cov: 33)
• Consequence: FOXC2 NM_005251.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.184

Genes affected

FOXC2 (HGNC:3801): (forkhead box C2) This gene belongs to the forkhead family of transcription factors which is characterized by a distinct DNA-binding forkhead domain. The specific function of this gene has not yet been determined; however, it may play a role in the development of mesenchymal tissues. [provided by RefSeq, Jul 2008]

FOXC2-AS1 (HGNC:50665): (FOXC2 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 16-86566986-G-T is Benign according to our data. Variant chr16-86566986-G-T is described in ClinVar as [Benign]. Clinvar id is 1245191.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOXC2	NM_005251.3	c.-350G>T		5_prime_UTR_variant	1/1	ENST00000649859.1	NP_005242.1
FOXC2-AS1	NR_125795.1	n.145+631C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOXC2	ENST00000649859.1	c.-350G>T		5_prime_UTR_variant	1/1		NM_005251.3	ENSP00000497759	P1
FOXC2-AS1	ENST00000563280.3	n.231+631C>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0435 AC: 6596 AN: 151616 Hom.: 329 Cov.: 33

Gnomad AFR AF: 0.0700

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.0823

Gnomad ASJ AF: 0.00809

Gnomad EAS AF: 0.220

Gnomad SAS AF: 0.0586

Gnomad FIN AF: 0.0438

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.00671

Gnomad OTH AF: 0.0362

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

GnomAD4 genome AF: 0.0436 AC: 6619 AN: 151724 Hom.: 330 Cov.: 33 AF XY: 0.0471 AC XY: 3492 AN XY: 74136

Gnomad4 AFR AF: 0.0701

Gnomad4 AMR AF: 0.0829

Gnomad4 ASJ AF: 0.00809

Gnomad4 EAS AF: 0.220

Gnomad4 SAS AF: 0.0588

Gnomad4 FIN AF: 0.0438

Gnomad4 NFE AF: 0.00671

Gnomad4 OTH AF: 0.0358

Alfa AF: 0.0250 Hom.: 11

Bravo AF: 0.0483

Asia WGS AF: 0.114 AC: 394 AN: 3464

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 18, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	3.2
DANN	Benign	0.91

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs78816814; hg19: chr16-86600592;