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

Variant summary

Our verdict is Benign. The variant received -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

Publications

52 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153756.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FNDC5	NM_153756.3	MANE Select	c.*1730C>T	3_prime_UTR	Exon 6 of 6	NP_715637.2	A0A0A0MRR6
FNDC5	NM_001441683.1		c.*1730C>T	3_prime_UTR	Exon 6 of 6	NP_001428612.1
FNDC5	NM_001436107.1		c.*1174C>T	3_prime_UTR	Exon 6 of 6	NP_001423036.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FNDC5	ENST00000373471.9	TSL:2 MANE Select	c.*1730C>T	3_prime_UTR	Exon 6 of 6	ENSP00000362570.5	A0A0A0MRR6
FNDC5	ENST00000481487.1	TSL:1	n.1267C>T	non_coding_transcript_exon	Exon 2 of 2
FNDC5	ENST00000710568.1		c.*1730C>T	3_prime_UTR	Exon 6 of 6	ENSP00000518350.1	Q8NAU1-5

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

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AF:

1.00

AC:

AN:

South Asian (SAS)

AF:

0.500

AC:

AN:

European-Finnish (FIN)

AF:

0.582

AC:

248

AN:

426

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.639

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.565

AC:

85914

AN:

152024

Hom.:

24479

Cov.:

AF XY:

0.562

AC XY:

41785

AN XY:

74302

show subpopulations

African (AFR)

AF:

0.489

AC:

20270

AN:

41460

American (AMR)

AF:

0.592

AC:

9042

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.505

AC:

1750

AN:

3466

East Asian (EAS)

AF:

0.741

AC:

3820

AN:

5158

South Asian (SAS)

AF:

0.567

AC:

2724

AN:

4808

European-Finnish (FIN)

AF:

0.559

AC:

5907

AN:

10568

Middle Eastern (MID)

AF:

0.558

AC:

164

AN:

294

European-Non Finnish (NFE)

AF:

0.594

AC:

40364

AN:

67966

Other (OTH)

AF:

0.593

AC:

1253

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1914

3828

5741

7655

9569

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

734

1468

2202

2936

3670

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.586

Hom.:

38295

Bravo

AF:

0.567

Asia WGS

AF:

0.680

AC:

2361

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

(source)

DANN

Benign

0.82

PhyloP100

0.72

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over