3-172210231-T-C

Variant names:

• chr3-172210231-T-C
• rs4610256
• NM_022763.4:c.188-16640T>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.188-16640T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.892 in 152,262 control chromosomes in the GnomAD database, including 60,828 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 (60828 hom., cov: 33)
• Consequence: FNDC3B NM_022763.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.88
• Publications: 1 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.942 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.188-16640T>C		intron	N/A	NP_073600.3
	FNDC3B	NM_001135095.2		c.188-16640T>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.188-16640T>C		intron	N/A	ENSP00000411242.2	Q53EP0-1
	FNDC3B	ENST00000336824.8	TSL:1	c.188-16640T>C		intron	N/A	ENSP00000338523.4	Q53EP0-1
	FNDC3B	ENST00000416957.5	TSL:1	c.188-16640T>C		intron	N/A	ENSP00000389094.1	Q53EP0-1

Frequencies

GnomAD3 genomes AF: 0.892 AC: 135689 AN: 152144 Hom.: 60793 Cov.: 33

Gnomad AFR AF: 0.950

Gnomad AMI AF: 0.843

Gnomad AMR AF: 0.808

Gnomad ASJ AF: 0.933

Gnomad EAS AF: 0.670

Gnomad SAS AF: 0.876

Gnomad FIN AF: 0.837

Gnomad MID AF: 0.937

Gnomad NFE AF: 0.900

Gnomad OTH AF: 0.899

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

GnomAD4 genome AF: 0.892 AC: 135776 AN: 152262 Hom.: 60828 Cov.: 33 AF XY: 0.885 AC XY: 65880 AN XY: 74438

African (AFR) AF: 0.950 AC: 39490 AN: 41580

American (AMR) AF: 0.807 AC: 12341 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.933 AC: 3239 AN: 3470

East Asian (EAS) AF: 0.670 AC: 3459 AN: 5162

South Asian (SAS) AF: 0.876 AC: 4234 AN: 4834

European-Finnish (FIN) AF: 0.837 AC: 8865 AN: 10594

Middle Eastern (MID) AF: 0.932 AC: 274 AN: 294

European-Non Finnish (NFE) AF: 0.900 AC: 61212 AN: 68012

Other (OTH) AF: 0.896 AC: 1895 AN: 2114

Alfa AF: 0.895 Hom.: 7901

Bravo AF: 0.892

Asia WGS AF: 0.773 AC: 2689 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.91
DANN	Benign	0.36
PhyloP100		-1.9
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: rs4610256; hg19: chr3-171928021;