rs12526577

Positions:

• chr6-159213576-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032532.3(FNDC1):​c.461-1369A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 151,934 control chromosomes in the GnomAD database, including 9,147 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 0.31 (9147 hom., cov: 31)
• Consequence: FNDC1 NM_032532.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.133

Genes affected

FNDC1 (HGNC:21184): (fibronectin type III domain containing 1) Predicted to act upstream of or within several processes, including cellular response to hypoxia; positive regulation of cardiac muscle cell apoptotic process; and positive regulation of protein phosphorylation. Located in nuclear speck. [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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.426 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FNDC1	NM_032532.3	c.461-1369A>G		intron_variant		ENST00000297267.14	NP_115921.2
FNDC1	XM_011536190.3	c.392-1369A>G		intron_variant			XP_011534492.1
FNDC1	XM_011536191.3	c.110-1369A>G		intron_variant			XP_011534493.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FNDC1	ENST00000297267.14	c.461-1369A>G		intron_variant		1	NM_032532.3	ENSP00000297267	P1
FNDC1	ENST00000329629.8	c.336-1369A>G		intron_variant		1		ENSP00000333297

Frequencies

GnomAD3 genomes AF: 0.314 AC: 47729 AN: 151816 Hom.: 9147 Cov.: 31

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.409

Gnomad AMR AF: 0.285

Gnomad ASJ AF: 0.412

Gnomad EAS AF: 0.215

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.430

Gnomad MID AF: 0.385

Gnomad NFE AF: 0.430

Gnomad OTH AF: 0.351

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

GnomAD4 genome AF: 0.314 AC: 47719 AN: 151934 Hom.: 9147 Cov.: 31 AF XY: 0.313 AC XY: 23275 AN XY: 74254

Gnomad4 AFR AF: 0.103

Gnomad4 AMR AF: 0.285

Gnomad4 ASJ AF: 0.412

Gnomad4 EAS AF: 0.216

Gnomad4 SAS AF: 0.328

Gnomad4 FIN AF: 0.430

Gnomad4 NFE AF: 0.430

Gnomad4 OTH AF: 0.347

Alfa AF: 0.409 Hom.: 16596

Bravo AF: 0.294

Asia WGS AF: 0.267 AC: 931 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.9
DANN	Benign	0.79

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: rs12526577; hg19: chr6-159634608;