chr3-172277815-C-T

Variant names:

• chr3-172277815-C-T
• rs4894535
• NM_022763.4:c.791-8111C>T

Variant summary

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

The NM_022763.4(FNDC3B):​c.791-8111C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 152,014 control chromosomes in the GnomAD database, including 2,982 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 0.19 (2982 hom., cov: 32)
• Consequence: FNDC3B NM_022763.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.531
• Publications: 38 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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FNDC3B	NM_022763.4	c.791-8111C>T		intron_variant	Intron 6 of 25	ENST00000415807.7	NP_073600.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FNDC3B	ENST00000415807.7	c.791-8111C>T		intron_variant	Intron 6 of 25	1	NM_022763.4	ENSP00000411242.2
FNDC3B	ENST00000336824.8	c.791-8111C>T		intron_variant	Intron 6 of 25	1		ENSP00000338523.4
FNDC3B	ENST00000416957.5	c.791-8111C>T		intron_variant	Intron 6 of 25	1		ENSP00000389094.1
FNDC3B	ENST00000469491.5	n.932-8111C>T		intron_variant	Intron 6 of 15	2

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29307 AN: 151896 Hom.: 2973 Cov.: 32

Gnomad AFR AF: 0.221

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.319

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.208

Gnomad MID AF: 0.124

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.168

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

GnomAD4 genome AF: 0.193 AC: 29352 AN: 152014 Hom.: 2982 Cov.: 32 AF XY: 0.197 AC XY: 14609 AN XY: 74336

African (AFR) AF: 0.221 AC: 9144 AN: 41444

American (AMR) AF: 0.247 AC: 3776 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.134 AC: 464 AN: 3468

East Asian (EAS) AF: 0.319 AC: 1649 AN: 5170

South Asian (SAS) AF: 0.197 AC: 947 AN: 4806

European-Finnish (FIN) AF: 0.208 AC: 2199 AN: 10582

Middle Eastern (MID) AF: 0.130 AC: 38 AN: 292

European-Non Finnish (NFE) AF: 0.156 AC: 10585 AN: 67958

Other (OTH) AF: 0.171 AC: 361 AN: 2106

Alfa AF: 0.166 Hom.: 9747

Bravo AF: 0.197

Asia WGS AF: 0.276 AC: 955 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.7
DANN	Benign	0.49
PhyloP100		0.53
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: rs4894535; hg19: chr3-171995605;