rs669552

chr3-172335874-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.1780+792A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 152,154 control chromosomes in the GnomAD database, including 2,651 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 0.17 (2651 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: FNDC3B NM_022763.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.09

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FNDC3B	NM_022763.4	c.1780+792A>G		intron_variant		ENST00000415807.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FNDC3B	ENST00000415807.7	c.1780+792A>G		intron_variant		1	NM_022763.4	P1
FNDC3B	ENST00000336824.8	c.1780+792A>G		intron_variant		1		P1
FNDC3B	ENST00000416957.5	c.1780+792A>G		intron_variant		1		P1
FNDC3B	ENST00000469491.5	n.1921+792A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25315 AN: 152036 Hom.: 2641 Cov.: 32

Gnomad AFR AF: 0.295

Gnomad AMI AF: 0.175

Gnomad AMR AF: 0.100

Gnomad ASJ AF: 0.162

Gnomad EAS AF: 0.0281

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.166

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

GnomAD4 genome AF: 0.167 AC: 25362 AN: 152154 Hom.: 2651 Cov.: 32 AF XY: 0.166 AC XY: 12378 AN XY: 74390

Gnomad4 AFR AF: 0.295

Gnomad4 AMR AF: 0.0999

Gnomad4 ASJ AF: 0.162

Gnomad4 EAS AF: 0.0282

Gnomad4 SAS AF: 0.134

Gnomad4 FIN AF: 0.144

Gnomad4 NFE AF: 0.120

Gnomad4 OTH AF: 0.165

Alfa AF: 0.128 Hom.: 1800

Bravo AF: 0.169

Asia WGS AF: 0.0990 AC: 346 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	5.4
Dann	Benign	0.79

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: rs669552; hg19: chr3-172053664;