chr3-172238631-T-C

Position:

• chr3-172238631-T-C

Variant summary

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

The NM_022763.4(FNDC3B):​c.265-8902T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 152,160 control chromosomes in the GnomAD database, including 1,963 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 0.15 (1963 hom., cov: 32)
• Consequence: FNDC3B NM_022763.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07

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 = 0.224 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FNDC3B	NM_022763.4	c.265-8902T>C		intron_variant		ENST00000415807.7	NP_073600.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FNDC3B	ENST00000415807.7	c.265-8902T>C		intron_variant		1	NM_022763.4	ENSP00000411242.2

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23248 AN: 152042 Hom.: 1963 Cov.: 32

Gnomad AFR AF: 0.228

Gnomad AMI AF: 0.166

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.206

Gnomad EAS AF: 0.137

Gnomad SAS AF: 0.209

Gnomad FIN AF: 0.0948

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.149

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

GnomAD4 genome AF: 0.153 AC: 23257 AN: 152160 Hom.: 1963 Cov.: 32 AF XY: 0.152 AC XY: 11276 AN XY: 74388

Gnomad4 AFR AF: 0.227

Gnomad4 AMR AF: 0.109

Gnomad4 ASJ AF: 0.206

Gnomad4 EAS AF: 0.137

Gnomad4 SAS AF: 0.209

Gnomad4 FIN AF: 0.0948

Gnomad4 NFE AF: 0.120

Gnomad4 OTH AF: 0.147

Alfa AF: 0.129 Hom.: 1600

Bravo AF: 0.156

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.46
DANN	Benign	0.48

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: rs7614432; hg19: chr3-171956421;