chr3-138948080-T-C

Variant names:

• chr3-138948080-T-C
• rs13064974
• NM_001040061.3:c.100+616T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

Genes affected

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

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001040061.3. 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
	FOXL2NB	NM_001040061.3	MANE Select	c.100+616T>C		intron	N/A	NP_001035150.1	Q6ZUU3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXL2NB	ENST00000383165.4	TSL:2 MANE Select	c.100+616T>C		intron	N/A	ENSP00000372651.3	Q6ZUU3
	FOXL2NB	ENST00000959845.1		c.100+616T>C		intron	N/A	ENSP00000629904.1
	FOXL2NB	ENST00000470680.5	TSL:3	n.100+616T>C		intron	N/A	ENSP00000418272.1	F8WBY5

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

African (AFR) AF: 0.394 AC: 3787 AN: 9610

American (AMR) AF: 0.0403 AC: 25 AN: 620

Ashkenazi Jewish (ASJ) AF: 0.0474 AC: 154 AN: 3250

East Asian (EAS) AF: 0.0177 AC: 39 AN: 2198

South Asian (SAS) AF: 0.0736 AC: 756 AN: 10278

European-Finnish (FIN) AF: 0.0753 AC: 14 AN: 186

Middle Eastern (MID) AF: 0.0733 AC: 74 AN: 1010

European-Non Finnish (NFE) AF: 0.0404 AC: 19573 AN: 484774

Other (OTH) AF: 0.0628 AC: 1086 AN: 17306

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

African (AFR) AF: 0.363 AC: 15036 AN: 41466

American (AMR) AF: 0.0625 AC: 956 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0536 AC: 186 AN: 3470

East Asian (EAS) AF: 0.0330 AC: 171 AN: 5188

South Asian (SAS) AF: 0.0727 AC: 351 AN: 4828

European-Finnish (FIN) AF: 0.0960 AC: 1020 AN: 10620

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0485 AC: 3300 AN: 68022

Other (OTH) AF: 0.114 AC: 241 AN: 2114

Alfa AF: 0.0626 Hom.: 1121

Bravo AF: 0.145

Asia WGS AF: 0.0820 AC: 288 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.5
DANN	Benign	0.58
PhyloP100		0.60
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: rs13064974; hg19: chr3-138666922;