Genetic Variant FNDC3B:c.188-14280G>A (chr3-172212591-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is . The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_022763.4(FNDC3B):c.188-14280G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.892 in 152,224 control chromosomes in the GnomAD database, including 60,786 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 0.89 ( 60786 hom., cov: 32)

Consequence

FNDC3B
NM_022763.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.33

Publications

2 publications found

Variant links:

Genes affected

FNDC3B (HGNC:24670): (fibronectin type III domain containing 3B) Enables RNA binding activity. Predicted to act upstream of or within several processes, including negative regulation of osteoblast differentiation; substrate adhesion-dependent cell spreading; and type II pneumocyte differentiation. Predicted to be located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

FNDC3B links:

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new If you want to explore the variant's impact on the transcript NM_022763.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.942 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022763.4. 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
	FNDC3B	NM_022763.4	MANE Select	c.188-14280G>A		intron	N/A	NP_073600.3
	FNDC3B	NM_001135095.2		c.188-14280G>A		intron	N/A	NP_001128567.1	Q53EP0-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FNDC3B	ENST00000415807.7	TSL:1 MANE Select	c.188-14280G>A	intron	N/A	ENSP00000411242.2	Q53EP0-1
FNDC3B	ENST00000336824.8	TSL:1	c.188-14280G>A	intron	N/A	ENSP00000338523.4	Q53EP0-1
FNDC3B	ENST00000416957.5	TSL:1	c.188-14280G>A	intron	N/A	ENSP00000389094.1	Q53EP0-1

Frequencies

GnomAD3 genomes

AF:

0.892

AC:

135631

AN:

152106

Hom.:

60751

Cov.:

show subpopulations

Gnomad AFR

AF:

0.950

Gnomad AMI

AF:

0.842

Gnomad AMR

AF:

0.808

Gnomad ASJ

AF:

0.933

Gnomad EAS

AF:

0.670

Gnomad SAS

AF:

0.876

Gnomad FIN

AF:

0.836

Gnomad MID

AF:

0.937

Gnomad NFE

AF:

0.900

Gnomad OTH

AF:

0.900

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

GnomAD4 genome

AF:

0.892

AC:

135718

AN:

152224

Hom.:

60786

Cov.:

AF XY:

0.885

AC XY:

65840

AN XY:

74394

show subpopulations

African (AFR)

AF:

0.950

AC:

39460

AN:

41554

American (AMR)

AF:

0.807

AC:

12333

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.933

AC:

3241

AN:

3472

East Asian (EAS)

AF:

0.670

AC:

3460

AN:

5164

South Asian (SAS)

AF:

0.876

AC:

4230

AN:

4830

European-Finnish (FIN)

AF:

0.836

AC:

8850

AN:

10580

Middle Eastern (MID)

AF:

0.932

AC:

274

AN:

294

European-Non Finnish (NFE)

AF:

0.900

AC:

61207

AN:

68024

Other (OTH)

AF:

0.897

AC:

1897

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

736

1472

2208

2944

3680

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

900

1800

2700

3600

4500

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.890

Hom.:

21337

Bravo

AF:

0.892

Asia WGS

AF:

0.771

AC:

2684

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.0090

(source)

DANN

Benign

0.65

PhyloP100

-1.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over