rs570549

Positions:

• chr3-172341331-G-A
• chr3-172341331-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.1971+100G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.686 in 861,140 control chromosomes in the GnomAD database, including 205,040 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 0.64 (32295 hom., cov: 33)
  • Exomes 𝑓: 0.69 (172745 hom.)
• Consequence: FNDC3B NM_022763.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.866

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.795 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FNDC3B	NM_022763.4	c.1971+100G>A		intron_variant		ENST00000415807.7	NP_073600.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FNDC3B	ENST00000415807.7	c.1971+100G>A		intron_variant		1	NM_022763.4	ENSP00000411242	P1
FNDC3B	ENST00000336824.8	c.1971+100G>A		intron_variant		1		ENSP00000338523	P1
FNDC3B	ENST00000416957.5	c.1971+100G>A		intron_variant		1		ENSP00000389094	P1

Frequencies

GnomAD3 genomes AF: 0.642 AC: 97541 AN: 151974 Hom.: 32271 Cov.: 33

Gnomad AFR AF: 0.480

Gnomad AMI AF: 0.766

Gnomad AMR AF: 0.709

Gnomad ASJ AF: 0.631

Gnomad EAS AF: 0.815

Gnomad SAS AF: 0.636

Gnomad FIN AF: 0.702

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.704

Gnomad OTH AF: 0.605

GnomAD4 exome AF: 0.695 AC: 492774 AN: 709048 Hom.: 172745 AF XY: 0.691 AC XY: 261933 AN XY: 378978

Gnomad4 AFR exome AF: 0.470

Gnomad4 AMR exome AF: 0.777

Gnomad4 ASJ exome AF: 0.651

Gnomad4 EAS exome AF: 0.827

Gnomad4 SAS exome AF: 0.629

Gnomad4 FIN exome AF: 0.691

Gnomad4 NFE exome AF: 0.702

Gnomad4 OTH exome AF: 0.674

GnomAD4 genome AF: 0.642 AC: 97598 AN: 152092 Hom.: 32295 Cov.: 33 AF XY: 0.643 AC XY: 47805 AN XY: 74340

Gnomad4 AFR AF: 0.479

Gnomad4 AMR AF: 0.709

Gnomad4 ASJ AF: 0.631

Gnomad4 EAS AF: 0.815

Gnomad4 SAS AF: 0.639

Gnomad4 FIN AF: 0.702

Gnomad4 NFE AF: 0.704

Gnomad4 OTH AF: 0.609

Alfa AF: 0.682 Hom.: 49266

Bravo AF: 0.637

Asia WGS AF: 0.712 AC: 2475 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.32
DANN	Benign	0.76

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

Publications

LitVar

Other links and lift over

dbSNP: rs570549; hg19: chr3-172059121;