rs1035550

Variant names:

• chr16-86569101-A-G
• rs1035550
• NM_005251.3:c.*260A>G

Your query was ambiguous. Multiple possible variants found:

• chr16-86569101-A-G
• chr16-86569101-A-C
• chr16-86569101-A-T

Variant summary

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

The NM_005251.3(FOXC2):​c.*260A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.901 in 581,892 control chromosomes in the GnomAD database, including 236,365 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.91 (62862 hom., cov: 32)
  • Exomes 𝑓: 0.90 (173503 hom.)
• Consequence: FOXC2 NM_005251.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.103
• Publications: 13 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 16-86569101-A-G is Benign according to our data. Variant chr16-86569101-A-G is described in ClinVar as Benign. ClinVar VariationId is 1294075.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.938 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005251.3. 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
	FOXC2	NM_005251.3	MANE Select	c.*260A>G		3_prime_UTR	Exon 1 of 1	NP_005242.1	Q99958

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXC2	ENST00000649859.1	MANE Select	c.*260A>G		3_prime_UTR	Exon 1 of 1	ENSP00000497759.1	Q99958
	FOXC2-AS1	ENST00000809048.1		n.-82T>C		upstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.908 AC: 138110 AN: 152114 Hom.: 62801 Cov.: 32

Gnomad AFR AF: 0.945

Gnomad AMI AF: 0.850

Gnomad AMR AF: 0.885

Gnomad ASJ AF: 0.856

Gnomad EAS AF: 0.847

Gnomad SAS AF: 0.924

Gnomad FIN AF: 0.947

Gnomad MID AF: 0.895

Gnomad NFE AF: 0.892

Gnomad OTH AF: 0.893

GnomAD4 exome AF: 0.898 AC: 385955 AN: 429660 Hom.: 173503 Cov.: 4 AF XY: 0.899 AC XY: 202646 AN XY: 225398

African (AFR) AF: 0.949 AC: 11131 AN: 11726

American (AMR) AF: 0.892 AC: 15767 AN: 17670

Ashkenazi Jewish (ASJ) AF: 0.856 AC: 10909 AN: 12746

East Asian (EAS) AF: 0.857 AC: 24065 AN: 28078

South Asian (SAS) AF: 0.923 AC: 41004 AN: 44412

European-Finnish (FIN) AF: 0.947 AC: 38587 AN: 40726

Middle Eastern (MID) AF: 0.876 AC: 1573 AN: 1796

European-Non Finnish (NFE) AF: 0.892 AC: 221538 AN: 248440

Other (OTH) AF: 0.888 AC: 21381 AN: 24066

GnomAD4 genome AF: 0.908 AC: 138230 AN: 152232 Hom.: 62862 Cov.: 32 AF XY: 0.909 AC XY: 67637 AN XY: 74414

African (AFR) AF: 0.945 AC: 39277 AN: 41548

American (AMR) AF: 0.885 AC: 13544 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.856 AC: 2968 AN: 3468

East Asian (EAS) AF: 0.847 AC: 4381 AN: 5172

South Asian (SAS) AF: 0.925 AC: 4454 AN: 4814

European-Finnish (FIN) AF: 0.947 AC: 10046 AN: 10610

Middle Eastern (MID) AF: 0.890 AC: 260 AN: 292

European-Non Finnish (NFE) AF: 0.892 AC: 60634 AN: 68002

Other (OTH) AF: 0.895 AC: 1891 AN: 2114

Alfa AF: 0.895 Hom.: 190083

Bravo AF: 0.904

Asia WGS AF: 0.871 AC: 3031 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.98
DANN	Benign	0.50
PhyloP100		0.10

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: rs1035550; hg19: chr16-86602707;