dbSNP rs3480: FNDC5:c.*1730C>T (chr1-32862564-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.722

Variant links:

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]

FNDC5 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 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_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.721 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
FNDC5	NM_153756.3 link	c.*1730C>T	3_prime_UTR_variant	Exon 6 of 6	ENST00000373471.9	NP_715637.2	Q8NAU1-1
FNDC5	NM_001171940.2 link	c.*1174C>T	3_prime_UTR_variant	Exon 6 of 6		NP_001165411.2	Q8NAU1-2
FNDC5	NM_001171941.3 link	c.*2046C>T	3_prime_UTR_variant	Exon 5 of 5		NP_001165412.1	Q8NAU1-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FNDC5	ENST00000373471 link	c.*1730C>T		3_prime_UTR_variant	Exon 6 of 6	2	NM_153756.3	ENSP00000362570.5		Q8NAU1-1A0A0A0MRR6

Frequencies

GnomAD3 genomes

AF:

0.565

AC:

85898

AN:

151906

Hom.:

24488

Cov.:

show subpopulations

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.:

Cov.:

AF XY:

0.577

AC XY:

172

AN XY:

298

show subpopulations

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.:

AF XY:

0.562

AC XY:

41785

AN XY:

74302

show subpopulations

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:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Feb 24, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over