Genetic Variant FNDC3B:c.1971+100G>C (chr3-172341331-G-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_022763.4(FNDC3B):c.1971+100G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000141 in 710,028 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

FNDC3B
NM_022763.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.866

Publications

7 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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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FNDC3B	NM_022763.4 link	c.1971+100G>C		intron_variant	Intron 17 of 25	ENST00000415807.7	NP_073600.3	Q53EP0-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
FNDC3B	ENST00000415807.7 link	c.1971+100G>C	intron_variant	Intron 17 of 25	1	NM_022763.4	ENSP00000411242.2	Q53EP0-1
FNDC3B	ENST00000336824.8 link	c.1971+100G>C	intron_variant	Intron 17 of 25	1		ENSP00000338523.4	Q53EP0-1
FNDC3B	ENST00000416957.5 link	c.1971+100G>C	intron_variant	Intron 17 of 25	1		ENSP00000389094.1	Q53EP0-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000141

AC:

AN:

710028

Hom.:

AF XY:

0.00

AC XY:

AN XY:

379508

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

19208

American (AMR)

AF:

0.00

AC:

AN:

43228

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20976

East Asian (EAS)

AF:

0.00

AC:

AN:

35958

South Asian (SAS)

AF:

0.0000144

AC:

AN:

69658

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48426

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3890

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

433114

Other (OTH)

AF:

0.00

AC:

AN:

35570

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.675

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.26

(source)

DANN

Benign

0.71

PhyloP100

-0.87

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over