chr3-172335874-A-G

Variant names:

• chr3-172335874-A-G
• rs669552
• NM_022763.4:c.1780+792A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
FNDC3B	NM_022763.4	c.1780+792A>G		intron_variant	Intron 15 of 25	ENST00000415807.7	NP_073600.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FNDC3B	ENST00000415807.7	c.1780+792A>G		intron_variant	Intron 15 of 25	1	NM_022763.4	ENSP00000411242.2

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

African (AFR) AF: 0.295 AC: 12250 AN: 41464

American (AMR) AF: 0.0999 AC: 1529 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.162 AC: 561 AN: 3472

East Asian (EAS) AF: 0.0282 AC: 146 AN: 5186

South Asian (SAS) AF: 0.134 AC: 645 AN: 4826

European-Finnish (FIN) AF: 0.144 AC: 1523 AN: 10588

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.120 AC: 8130 AN: 67998

Other (OTH) AF: 0.165 AC: 349 AN: 2114

Alfa AF: 0.130 Hom.: 2214

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
PhyloP100		1.1
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: rs669552; hg19: chr3-172053664;