rs6445044

Positions:

• chr3-172202779-G-A
• chr3-172202779-G-C

Variant summary

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

The NM_022763.4(FNDC3B):​c.188-24092G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.891 in 152,244 control chromosomes in the GnomAD database, including 60,750 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 0.89 (60750 hom., cov: 32)
• Consequence: FNDC3B NM_022763.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.317

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.941 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FNDC3B	NM_022763.4	c.188-24092G>A		intron_variant		ENST00000415807.7	NP_073600.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FNDC3B	ENST00000415807.7	c.188-24092G>A		intron_variant		1	NM_022763.4	ENSP00000411242	P1

Frequencies

GnomAD3 genomes AF: 0.891 AC: 135598 AN: 152126 Hom.: 60715 Cov.: 32

Gnomad AFR AF: 0.949

Gnomad AMI AF: 0.841

Gnomad AMR AF: 0.807

Gnomad ASJ AF: 0.933

Gnomad EAS AF: 0.669

Gnomad SAS AF: 0.876

Gnomad FIN AF: 0.837

Gnomad MID AF: 0.937

Gnomad NFE AF: 0.900

Gnomad OTH AF: 0.898

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

GnomAD4 genome AF: 0.891 AC: 135685 AN: 152244 Hom.: 60750 Cov.: 32 AF XY: 0.885 AC XY: 65831 AN XY: 74420

Gnomad4 AFR AF: 0.949

Gnomad4 AMR AF: 0.807

Gnomad4 ASJ AF: 0.933

Gnomad4 EAS AF: 0.669

Gnomad4 SAS AF: 0.875

Gnomad4 FIN AF: 0.837

Gnomad4 NFE AF: 0.900

Gnomad4 OTH AF: 0.896

Alfa AF: 0.877 Hom.: 10005

Bravo AF: 0.891

Asia WGS AF: 0.773 AC: 2690 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	0.75
DANN	Benign	0.66

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: rs6445044; hg19: chr3-171920569;