NM_032532.3:c.460+5464C>T

Variant names:

• chr6-159206045-C-T
• rs294917
• NM_032532.3:c.460+5464C>T

Variant summary

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

The NM_032532.3(FNDC1):​c.460+5464C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 152,122 control chromosomes in the GnomAD database, including 6,420 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 0.28 (6420 hom., cov: 33)
• Consequence: FNDC1 NM_032532.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.487
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.633 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FNDC1	NM_032532.3	c.460+5464C>T		intron_variant	Intron 4 of 22	ENST00000297267.14	NP_115921.2
FNDC1	XM_011536190.3	c.391+5963C>T		intron_variant	Intron 3 of 21		XP_011534492.1
FNDC1	XM_011536191.3	c.110-8900C>T		intron_variant	Intron 1 of 19		XP_011534493.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FNDC1	ENST00000297267.14	c.460+5464C>T		intron_variant	Intron 4 of 22	1	NM_032532.3	ENSP00000297267.9
FNDC1	ENST00000329629.8	c.334+5464C>T		intron_variant	Intron 3 of 20	1		ENSP00000333297.8

Frequencies

GnomAD3 genomes AF: 0.277 AC: 42135 AN: 152004 Hom.: 6412 Cov.: 33

Gnomad AFR AF: 0.337

Gnomad AMI AF: 0.226

Gnomad AMR AF: 0.248

Gnomad ASJ AF: 0.207

Gnomad EAS AF: 0.652

Gnomad SAS AF: 0.302

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.256

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

GnomAD4 genome AF: 0.277 AC: 42172 AN: 152122 Hom.: 6420 Cov.: 33 AF XY: 0.281 AC XY: 20870 AN XY: 74366

African (AFR) AF: 0.337 AC: 13992 AN: 41482

American (AMR) AF: 0.247 AC: 3784 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.207 AC: 720 AN: 3472

East Asian (EAS) AF: 0.651 AC: 3360 AN: 5158

South Asian (SAS) AF: 0.302 AC: 1459 AN: 4824

European-Finnish (FIN) AF: 0.233 AC: 2463 AN: 10572

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.229 AC: 15575 AN: 68000

Other (OTH) AF: 0.256 AC: 541 AN: 2112

Alfa AF: 0.251 Hom.: 827

Bravo AF: 0.283

Asia WGS AF: 0.430 AC: 1493 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	7.0
DANN	Benign	0.34
PhyloP100		0.49
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: rs294917; hg19: chr6-159627077;