3-172370108-T-C

Variant names:

• chr3-172370108-T-C
• rs660239
• NM_022763.4:c.3008+7263T>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.3008+7263T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.43 in 152,028 control chromosomes in the GnomAD database, including 16,050 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 0.43 (16050 hom., cov: 32)
• Consequence: FNDC3B NM_022763.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.448
• Publications: 3 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.564 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022763.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FNDC3B	NM_022763.4	MANE Select	c.3008+7263T>C		intron	N/A	NP_073600.3
	FNDC3B	NM_001135095.2		c.3008+7263T>C		intron	N/A	NP_001128567.1	Q53EP0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FNDC3B	ENST00000415807.7	TSL:1 MANE Select	c.3008+7263T>C		intron	N/A	ENSP00000411242.2	Q53EP0-1
	FNDC3B	ENST00000336824.8	TSL:1	c.3008+7263T>C		intron	N/A	ENSP00000338523.4	Q53EP0-1
	FNDC3B	ENST00000416957.5	TSL:1	c.3008+7263T>C		intron	N/A	ENSP00000389094.1	Q53EP0-1

Frequencies

GnomAD3 genomes AF: 0.431 AC: 65420 AN: 151910 Hom.: 16051 Cov.: 32

Gnomad AFR AF: 0.207

Gnomad AMI AF: 0.600

Gnomad AMR AF: 0.431

Gnomad ASJ AF: 0.485

Gnomad EAS AF: 0.266

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.519

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.569

Gnomad OTH AF: 0.400

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

GnomAD4 genome AF: 0.430 AC: 65439 AN: 152028 Hom.: 16050 Cov.: 32 AF XY: 0.425 AC XY: 31564 AN XY: 74318

African (AFR) AF: 0.207 AC: 8571 AN: 41474

American (AMR) AF: 0.431 AC: 6578 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.485 AC: 1684 AN: 3472

East Asian (EAS) AF: 0.266 AC: 1376 AN: 5168

South Asian (SAS) AF: 0.329 AC: 1585 AN: 4816

European-Finnish (FIN) AF: 0.519 AC: 5476 AN: 10542

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.569 AC: 38677 AN: 67966

Other (OTH) AF: 0.399 AC: 843 AN: 2112

Alfa AF: 0.523 Hom.: 90959

Bravo AF: 0.416

Asia WGS AF: 0.316 AC: 1097 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	16
DANN	Benign	0.41
PhyloP100		0.45
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: rs660239; hg19: chr3-172087898;