3-172062973-A-G

Variant summary

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

The NM_022763.4(FNDC3B):c.-29+23202A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.534 in 152,004 control chromosomes in the GnomAD database, including 22,027 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 0.53 (22027 hom., cov: 32)
• Consequence: FNDC3B NM_022763.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.581 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FNDC3B	NM_022763.4	c.-29+23202A>G		intron_variant		ENST00000415807.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FNDC3B	ENST00000415807.7	c.-29+23202A>G		intron_variant		1	NM_022763.4	P1

Frequencies

GnomAD3 genomes AF: 0.534 AC: 81087 AN: 151886 Hom.: 22000 Cov.: 32

Gnomad AFR AF: 0.432

Gnomad AMI AF: 0.642

Gnomad AMR AF: 0.591

Gnomad ASJ AF: 0.501

Gnomad EAS AF: 0.539

Gnomad SAS AF: 0.470

Gnomad FIN AF: 0.600

Gnomad MID AF: 0.433

Gnomad NFE AF: 0.577

Gnomad OTH AF: 0.558

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

GnomAD4 genome AF: 0.534 AC: 81154 AN: 152004 Hom.: 22027 Cov.: 32 AF XY: 0.537 AC XY: 39873 AN XY: 74298

Gnomad4 AFR AF: 0.432

Gnomad4 AMR AF: 0.591

Gnomad4 ASJ AF: 0.501

Gnomad4 EAS AF: 0.538

Gnomad4 SAS AF: 0.471

Gnomad4 FIN AF: 0.600

Gnomad4 NFE AF: 0.577

Gnomad4 OTH AF: 0.563

Alfa AF: 0.564 Hom.: 43055

Bravo AF: 0.530

Asia WGS AF: 0.549 AC: 1908 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.71
Dann	Benign	0.83
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs4894796; hg19: chr3-171780763;