rs6445055

Positions:

• chr3-172274597-G-A
• chr3-172274597-G-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.341 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FNDC3B	NM_022763.4	c.791-11329G>A		intron_variant		ENST00000415807.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FNDC3B	ENST00000415807.7	c.791-11329G>A		intron_variant		1	NM_022763.4	P1
FNDC3B	ENST00000336824.8	c.791-11329G>A		intron_variant		1		P1
FNDC3B	ENST00000416957.5	c.791-11329G>A		intron_variant		1		P1
FNDC3B	ENST00000469491.5	n.932-11329G>A		intron_variant, non_coding_transcript_variant		2

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

Gnomad4 AFR AF: 0.346

Gnomad4 AMR AF: 0.266

Gnomad4 ASJ AF: 0.136

Gnomad4 EAS AF: 0.321

Gnomad4 SAS AF: 0.201

Gnomad4 FIN AF: 0.211

Gnomad4 NFE AF: 0.170

Gnomad4 OTH AF: 0.213

Alfa AF: 0.145 Hom.: 346

Bravo AF: 0.246

Asia WGS AF: 0.281 AC: 975 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.3
DANN	Benign	0.18
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs6445055; hg19: chr3-171992387;