chr1-32862564-G-A

Position:

• chr1-32862564-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_153756.3(FNDC5):​c.*1730C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.565 in 152,504 control chromosomes in the GnomAD database, including 24,559 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.57 (24479 hom., cov: 32)
  • Exomes 𝑓: 0.59 (80 hom.)
• Consequence: FNDC5 NM_153756.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.722

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 1-32862564-G-A is Benign according to our data. Variant chr1-32862564-G-A is described in ClinVar as [Benign]. Clinvar id is 1227050.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.721 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FNDC5	NM_153756.3	c.*1730C>T		3_prime_UTR_variant	6/6	ENST00000373471.9
FNDC5	NM_001171940.2	c.*1174C>T		3_prime_UTR_variant	6/6
FNDC5	NM_001171941.3	c.*2046C>T		3_prime_UTR_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FNDC5	ENST00000373471.9	c.*1730C>T		3_prime_UTR_variant	6/6	2	NM_153756.3

Frequencies

GnomAD3 genomes AF: 0.565 AC: 85898 AN: 151906 Hom.: 24488 Cov.: 32

Gnomad AFR AF: 0.490

Gnomad AMI AF: 0.681

Gnomad AMR AF: 0.592

Gnomad ASJ AF: 0.505

Gnomad EAS AF: 0.741

Gnomad SAS AF: 0.568

Gnomad FIN AF: 0.559

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.594

Gnomad OTH AF: 0.590

GnomAD4 exome AF: 0.588 AC: 282 AN: 480 Hom.: 80 Cov.: 0 AF XY: 0.577 AC XY: 172 AN XY: 298

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.582

Gnomad4 NFE exome AF: 0.639

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.565 AC: 85914 AN: 152024 Hom.: 24479 Cov.: 32 AF XY: 0.562 AC XY: 41785 AN XY: 74302

Gnomad4 AFR AF: 0.489

Gnomad4 AMR AF: 0.592

Gnomad4 ASJ AF: 0.505

Gnomad4 EAS AF: 0.741

Gnomad4 SAS AF: 0.567

Gnomad4 FIN AF: 0.559

Gnomad4 NFE AF: 0.594

Gnomad4 OTH AF: 0.593

Alfa AF: 0.589 Hom.: 26125

Bravo AF: 0.567

Asia WGS AF: 0.680 AC: 2361 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 24, 2021

This variant is associated with the following publications: (PMID: 30389552) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	15
DANN	Benign	0.82

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: rs3480; hg19: chr1-33328165; COSMIC: COSV65105648; COSMIC: COSV65105648;