dbSNP rs704795: FNDC4:c.455-149C>T (chr2-27493627-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_022823.3(FNDC4):c.455-149C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.393 in 727,048 control chromosomes in the GnomAD database, including 60,546 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 0.45 ( 16460 hom., cov: 32)

Exomes 𝑓: 0.38 ( 44086 hom. )

Consequence

FNDC4
NM_022823.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.780

Publications

29 publications found

Variant links:

Genes affected

FNDC4 (HGNC:20239): (fibronectin type III domain containing 4) Involved in response to transforming growth factor beta. Predicted to be located in endoplasmic reticulum and extracellular space. Predicted to be active in extracellular region and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

FNDC4 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.609 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
FNDC4	NM_022823.3 link	c.455-149C>T	intron_variant	Intron 4 of 6	ENST00000264703.4	NP_073734.1	Q9H6D8
FNDC4	XM_047445471.1 link	c.455-149C>T	intron_variant	Intron 3 of 5		XP_047301427.1
FNDC4	XM_005264499.5 link	c.455-149C>T	intron_variant	Intron 4 of 5		XP_005264556.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
FNDC4	ENST00000264703.4 link	c.455-149C>T	intron_variant	Intron 4 of 6	1	NM_022823.3	ENSP00000264703.3	Q9H6D8
FNDC4	ENST00000476197.1 link	n.588-149C>T	intron_variant	Intron 3 of 4	2
FNDC4	ENST00000491414.5 link	n.980-149C>T	intron_variant	Intron 3 of 4	5

Frequencies

GnomAD3 genomes

AF:

0.449

AC:

68241

AN:

151934

Hom.:

16418

Cov.:

show subpopulations

Gnomad AFR

AF:

0.615

Gnomad AMI

AF:

0.220

Gnomad AMR

AF:

0.466

Gnomad ASJ

AF:

0.339

Gnomad EAS

AF:

0.151

Gnomad SAS

AF:

0.423

Gnomad FIN

AF:

0.430

Gnomad MID

AF:

0.367

Gnomad NFE

AF:

0.383

Gnomad OTH

AF:

0.398

GnomAD4 exome

AF:

0.378

AC:

217139

AN:

574996

Hom.:

44086

AF XY:

0.377

AC XY:

115076

AN XY:

304842

show subpopulations

African (AFR)

AF:

0.610

AC:

9389

AN:

15394

American (AMR)

AF:

0.537

AC:

14914

AN:

27778

Ashkenazi Jewish (ASJ)

AF:

0.334

AC:

5291

AN:

15848

East Asian (EAS)

AF:

0.129

AC:

4383

AN:

34034

South Asian (SAS)

AF:

0.413

AC:

22908

AN:

55404

European-Finnish (FIN)

AF:

0.429

AC:

16728

AN:

39006

Middle Eastern (MID)

AF:

0.319

AC:

764

AN:

2392

European-Non Finnish (NFE)

AF:

0.370

AC:

131042

AN:

354582

Other (OTH)

AF:

0.384

AC:

11720

AN:

30558

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

6661

13323

19984

26646

33307

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1448

2896

4344

5792

7240

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.449

AC:

68345

AN:

152052

Hom.:

16460

Cov.:

AF XY:

0.449

AC XY:

33338

AN XY:

74326

show subpopulations

African (AFR)

AF:

0.615

AC:

25516

AN:

41462

American (AMR)

AF:

0.466

AC:

7127

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.339

AC:

1175

AN:

3468

East Asian (EAS)

AF:

0.151

AC:

782

AN:

5178

South Asian (SAS)

AF:

0.424

AC:

2037

AN:

4808

European-Finnish (FIN)

AF:

0.430

AC:

4543

AN:

10574

Middle Eastern (MID)

AF:

0.374

AC:

110

AN:

294

European-Non Finnish (NFE)

AF:

0.383

AC:

26007

AN:

67968

Other (OTH)

AF:

0.402

AC:

847

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1814

3628

5442

7256

9070

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

612

1224

1836

2448

3060

<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:

0.397

Hom.:

15709

Bravo

AF:

0.458

Asia WGS

AF:

0.353

AC:

1228

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

0.68

(source)

DANN

Benign

0.75

PhyloP100

-0.78

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over