rs294882

chr6-159181969-T-Cchr6-159181969-T-G

Variant summary

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

The NM_032532.3(FNDC1):c.109+12264T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.54 in 151,946 control chromosomes in the GnomAD database, including 22,444 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 0.54 (22444 hom., cov: 31)
• Consequence: FNDC1 NM_032532.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.327

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.591 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FNDC1	NM_032532.3	c.109+12264T>C		intron_variant		ENST00000297267.14
FNDC1	XM_011536190.3	c.109+12264T>C		intron_variant
FNDC1	XM_011536191.3	c.109+12264T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FNDC1	ENST00000297267.14	c.109+12264T>C		intron_variant		1	NM_032532.3	P1

Frequencies

GnomAD3 genomes AF: 0.540 AC: 81991 AN: 151828 Hom.: 22424 Cov.: 31

Gnomad AFR AF: 0.597

Gnomad AMI AF: 0.524

Gnomad AMR AF: 0.441

Gnomad ASJ AF: 0.564

Gnomad EAS AF: 0.508

Gnomad SAS AF: 0.493

Gnomad FIN AF: 0.528

Gnomad MID AF: 0.634

Gnomad NFE AF: 0.533

Gnomad OTH AF: 0.550

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

GnomAD4 genome AF: 0.540 AC: 82045 AN: 151946 Hom.: 22444 Cov.: 31 AF XY: 0.537 AC XY: 39876 AN XY: 74272

Gnomad4 AFR AF: 0.597

Gnomad4 AMR AF: 0.441

Gnomad4 ASJ AF: 0.564

Gnomad4 EAS AF: 0.507

Gnomad4 SAS AF: 0.494

Gnomad4 FIN AF: 0.528

Gnomad4 NFE AF: 0.533

Gnomad4 OTH AF: 0.543

Alfa AF: 0.537 Hom.: 5355

Bravo AF: 0.532

Asia WGS AF: 0.486 AC: 1693 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	2.6
Dann	Benign	0.62

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: rs294882; hg19: chr6-159603001;