rs13064974

Positions:

• chr3-138948080-T-C
• chr3-138948080-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001040061.3(FOXL2NB):​c.100+616T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0688 in 681,452 control chromosomes in the GnomAD database, including 4,234 homozygotes. 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: 𝑓 0.14 (2932 hom., cov: 32)
  • Exomes 𝑓: 0.048 (1302 hom.)
• Consequence: FOXL2NB NM_001040061.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.605

Genes affected

FOXL2NB (HGNC:34428): (FOXL2 neighbor) Located in fibrillar center. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.358 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOXL2NB	NM_001040061.3	c.100+616T>C		intron_variant		ENST00000383165.4	NP_001035150.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOXL2NB	ENST00000383165.4	c.100+616T>C		intron_variant		2	NM_001040061.3	ENSP00000372651	P1
FOXL2NB	ENST00000470680.5	c.100+616T>C		intron_variant, NMD_transcript_variant		3		ENSP00000418272
FOXL2NB	ENST00000498709.1	n.396+73T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21296 AN: 152102 Hom.: 2920 Cov.: 32

Gnomad AFR AF: 0.362

Gnomad AMI AF: 0.0910

Gnomad AMR AF: 0.0626

Gnomad ASJ AF: 0.0536

Gnomad EAS AF: 0.0329

Gnomad SAS AF: 0.0728

Gnomad FIN AF: 0.0960

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0485

Gnomad OTH AF: 0.109

GnomAD4 exome AF: 0.0482 AC: 25508 AN: 529232 Hom.: 1302 AF XY: 0.0485 AC XY: 12013 AN XY: 247820

Gnomad4 AFR exome AF: 0.394

Gnomad4 AMR exome AF: 0.0403

Gnomad4 ASJ exome AF: 0.0474

Gnomad4 EAS exome AF: 0.0177

Gnomad4 SAS exome AF: 0.0736

Gnomad4 FIN exome AF: 0.0753

Gnomad4 NFE exome AF: 0.0404

Gnomad4 OTH exome AF: 0.0628

GnomAD4 genome AF: 0.140 AC: 21363 AN: 152220 Hom.: 2932 Cov.: 32 AF XY: 0.139 AC XY: 10324 AN XY: 74440

Gnomad4 AFR AF: 0.363

Gnomad4 AMR AF: 0.0625

Gnomad4 ASJ AF: 0.0536

Gnomad4 EAS AF: 0.0330

Gnomad4 SAS AF: 0.0727

Gnomad4 FIN AF: 0.0960

Gnomad4 NFE AF: 0.0485

Gnomad4 OTH AF: 0.114

Alfa AF: 0.0528 Hom.: 557

Bravo AF: 0.145

Asia WGS AF: 0.0820 AC: 288 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.5
DANN	Benign	0.58

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

Publications

LitVar

Other links and lift over

dbSNP: rs13064974; hg19: chr3-138666922;