1-32869438-G-T

Variant names:

• chr1-32869438-G-T
• rs1746661
• NM_153756.3:c.95-441C>A

Variant summary

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

The NM_153756.3(FNDC5):​c.95-441C>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 152,276 control chromosomes in the GnomAD database, including 1,925 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 (1925 hom., cov: 32)
• Consequence: FNDC5 NM_153756.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.925
• Publications: 22 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.22 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FNDC5	NM_153756.3	MANE Select	c.95-441C>A		intron	N/A	NP_715637.2	A0A0A0MRR6
	FNDC5	NM_001441683.1		c.239-441C>A		intron	N/A	NP_001428612.1
	FNDC5	NM_001436107.1		c.95-441C>A		intron	N/A	NP_001423036.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FNDC5	ENST00000373471.9	TSL:2 MANE Select	c.95-441C>A		intron	N/A	ENSP00000362570.5	A0A0A0MRR6
	FNDC5	ENST00000496770.1	TSL:1	c.-127-445C>A		intron	N/A	ENSP00000476320.1	Q8NAU1-3
	FNDC5	ENST00000710568.1		c.239-441C>A		intron	N/A	ENSP00000518350.1	Q8NAU1-5

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21648 AN: 152158 Hom.: 1928 Cov.: 32

Gnomad AFR AF: 0.0357

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.210

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.184

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.152

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

GnomAD4 genome AF: 0.142 AC: 21649 AN: 152276 Hom.: 1925 Cov.: 32 AF XY: 0.145 AC XY: 10829 AN XY: 74454

African (AFR) AF: 0.0356 AC: 1480 AN: 41574

American (AMR) AF: 0.130 AC: 1985 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.217 AC: 754 AN: 3468

East Asian (EAS) AF: 0.210 AC: 1089 AN: 5178

South Asian (SAS) AF: 0.231 AC: 1116 AN: 4830

European-Finnish (FIN) AF: 0.184 AC: 1954 AN: 10604

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.188 AC: 12785 AN: 67998

Other (OTH) AF: 0.149 AC: 316 AN: 2114

Alfa AF: 0.165 Hom.: 2944

Bravo AF: 0.132

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	7.5
DANN	Benign	0.65
PhyloP100		0.93
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1746661; hg19: chr1-33335039;