rs1499812

Variant names:

• chr3-172042418-G-C
• rs1499812
• NM_022763.4:c.-29+2647G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022763.4(FNDC3B):​c.-29+2647G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.679 in 152,002 control chromosomes in the GnomAD database, including 35,221 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 0.68 (35221 hom., cov: 31)
• Consequence: FNDC3B NM_022763.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.629
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.799 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FNDC3B	NM_022763.4	c.-29+2647G>C		intron_variant	Intron 1 of 25	ENST00000415807.7	NP_073600.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FNDC3B	ENST00000415807.7	c.-29+2647G>C		intron_variant	Intron 1 of 25	1	NM_022763.4	ENSP00000411242.2

Frequencies

GnomAD3 genomes AF: 0.679 AC: 103107 AN: 151882 Hom.: 35164 Cov.: 31

Gnomad AFR AF: 0.691

Gnomad AMI AF: 0.657

Gnomad AMR AF: 0.735

Gnomad ASJ AF: 0.610

Gnomad EAS AF: 0.821

Gnomad SAS AF: 0.577

Gnomad FIN AF: 0.717

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.654

Gnomad OTH AF: 0.678

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

GnomAD4 genome AF: 0.679 AC: 103229 AN: 152002 Hom.: 35221 Cov.: 31 AF XY: 0.684 AC XY: 50818 AN XY: 74326

African (AFR) AF: 0.692 AC: 28664 AN: 41442

American (AMR) AF: 0.735 AC: 11234 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.610 AC: 2118 AN: 3472

East Asian (EAS) AF: 0.820 AC: 4243 AN: 5176

South Asian (SAS) AF: 0.578 AC: 2782 AN: 4812

European-Finnish (FIN) AF: 0.717 AC: 7579 AN: 10570

Middle Eastern (MID) AF: 0.558 AC: 164 AN: 294

European-Non Finnish (NFE) AF: 0.654 AC: 44408 AN: 67936

Other (OTH) AF: 0.682 AC: 1439 AN: 2110

Alfa AF: 0.676 Hom.: 4352

Bravo AF: 0.684

Asia WGS AF: 0.725 AC: 2520 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.5
DANN	Benign	0.29
PhyloP100		-0.63
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: rs1499812; hg19: chr3-171760208;