1-32871355-G-T

Position:

• chr1-32871355-G-T

Variant summary

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

The ENST00000496770.1(FNDC5):​c.-128+1039C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 152,072 control chromosomes in the GnomAD database, including 1,913 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 0.14 (1913 hom., cov: 30)
• Consequence: FNDC5 ENST00000496770.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.398

Genes affected

FNDC5 (HGNC:20240): (fibronectin type III domain containing 5) This gene encodes a secreted protein that is released from muscle cells during exercise. The encoded protein may participate in the development of brown fat. Translation of the precursor protein initiates at a non-AUG start codon at a position that is conserved as an AUG start codon in other organisms. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FNDC5	NM_001171941.3	c.-128+1039C>A		intron_variant			NP_001165412.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FNDC5	ENST00000496770.1	c.-128+1039C>A		intron_variant		1		ENSP00000476320
FNDC5	ENST00000465346.1	n.90-379C>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21630 AN: 151954 Hom.: 1916 Cov.: 30

Gnomad AFR AF: 0.0363

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.211

Gnomad SAS AF: 0.229

Gnomad FIN AF: 0.185

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.151

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

GnomAD4 genome AF: 0.142 AC: 21631 AN: 152072 Hom.: 1913 Cov.: 30 AF XY: 0.145 AC XY: 10807 AN XY: 74310

Gnomad4 AFR AF: 0.0362

Gnomad4 AMR AF: 0.129

Gnomad4 ASJ AF: 0.218

Gnomad4 EAS AF: 0.211

Gnomad4 SAS AF: 0.229

Gnomad4 FIN AF: 0.185

Gnomad4 NFE AF: 0.188

Gnomad4 OTH AF: 0.149

Alfa AF: 0.168 Hom.: 394

Bravo AF: 0.132

Asia WGS AF: 0.167 AC: 583 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	3.7
DANN	Benign	0.54

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1570569; hg19: chr1-33336956;