3-172274597-G-A

Variant names:

• chr3-172274597-G-A
• rs6445055
• NM_022763.4:c.791-11329G>A

Variant summary

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

The NM_022763.4(FNDC3B):​c.791-11329G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 152,072 control chromosomes in the GnomAD database, including 4,729 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 0.24 (4729 hom., cov: 32)
• Consequence: FNDC3B NM_022763.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0280
• Publications: 18 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.341 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FNDC3B	NM_022763.4	MANE Select	c.791-11329G>A		intron	N/A	NP_073600.3
	FNDC3B	NM_001135095.2		c.791-11329G>A		intron	N/A	NP_001128567.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FNDC3B	ENST00000415807.7	TSL:1 MANE Select	c.791-11329G>A		intron	N/A	ENSP00000411242.2
	FNDC3B	ENST00000336824.8	TSL:1	c.791-11329G>A		intron	N/A	ENSP00000338523.4
	FNDC3B	ENST00000416957.5	TSL:1	c.791-11329G>A		intron	N/A	ENSP00000389094.1

Frequencies

GnomAD3 genomes AF: 0.237 AC: 35967 AN: 151954 Hom.: 4719 Cov.: 32

Gnomad AFR AF: 0.346

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.321

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.211

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.209

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

GnomAD4 genome AF: 0.237 AC: 36018 AN: 152072 Hom.: 4729 Cov.: 32 AF XY: 0.238 AC XY: 17699 AN XY: 74344

African (AFR) AF: 0.346 AC: 14324 AN: 41448

American (AMR) AF: 0.266 AC: 4065 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 472 AN: 3470

East Asian (EAS) AF: 0.321 AC: 1659 AN: 5170

South Asian (SAS) AF: 0.201 AC: 972 AN: 4824

European-Finnish (FIN) AF: 0.211 AC: 2227 AN: 10572

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.170 AC: 11559 AN: 67988

Other (OTH) AF: 0.213 AC: 450 AN: 2108

Alfa AF: 0.192 Hom.: 4679

Bravo AF: 0.246

Asia WGS AF: 0.281 AC: 975 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.3
DANN	Benign	0.18
PhyloP100		0.028
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs6445055; hg19: chr3-171992387;