Genetic Variant NM_022823.3:c.670-71G>A (chr2-27492549-C-T) – 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.670-71G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.382 in 1,585,768 control chromosomes in the GnomAD database, including 119,086 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 0.37 ( 11012 hom., cov: 31)

Exomes 𝑓: 0.38 ( 108074 hom. )

Consequence

FNDC4
NM_022823.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.209

Publications

50 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=-0.91).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.428 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022823.3. 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
	FNDC4	NM_022823.3	MANE Select	c.670-71G>A		intron	N/A	NP_073734.1	Q9H6D8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FNDC4	ENST00000264703.4	TSL:1 MANE Select	c.670-71G>A	intron	N/A	ENSP00000264703.3	Q9H6D8
FNDC4	ENST00000934125.1		c.670-71G>A	intron	N/A	ENSP00000604184.1
FNDC4	ENST00000951222.1		c.670-71G>A	intron	N/A	ENSP00000621281.1

Frequencies

GnomAD3 genomes

AF:

0.375

AC:

56896

AN:

151834

Hom.:

10991

Cov.:

show subpopulations

Gnomad AFR

AF:

0.362

Gnomad AMI

AF:

0.221

Gnomad AMR

AF:

0.436

Gnomad ASJ

AF:

0.334

Gnomad EAS

AF:

0.150

Gnomad SAS

AF:

0.423

Gnomad FIN

AF:

0.430

Gnomad MID

AF:

0.354

Gnomad NFE

AF:

0.378

Gnomad OTH

AF:

0.350

GnomAD4 exome

AF:

0.383

AC:

548733

AN:

1433816

Hom.:

108074

Cov.:

AF XY:

0.382

AC XY:

273465

AN XY:

715074

show subpopulations

African (AFR)

AF:

0.354

AC:

11644

AN:

32864

American (AMR)

AF:

0.538

AC:

24061

AN:

44700

Ashkenazi Jewish (ASJ)

AF:

0.337

AC:

8738

AN:

25954

East Asian (EAS)

AF:

0.133

AC:

5264

AN:

39556

South Asian (SAS)

AF:

0.416

AC:

35682

AN:

85674

European-Finnish (FIN)

AF:

0.432

AC:

23065

AN:

53400

Middle Eastern (MID)

AF:

0.335

AC:

1915

AN:

5718

European-Non Finnish (NFE)

AF:

0.383

AC:

416511

AN:

1086474

Other (OTH)

AF:

0.367

AC:

21853

AN:

59476

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

18518

37036

55554

74072

92590

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13100

26200

39300

52400

65500

<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:

0.375

AC:

56948

AN:

151952

Hom.:

11012

Cov.:

AF XY:

0.375

AC XY:

27877

AN XY:

74302

show subpopulations

African (AFR)

AF:

0.362

AC:

14987

AN:

41404

American (AMR)

AF:

0.437

AC:

6677

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.334

AC:

1157

AN:

3462

East Asian (EAS)

AF:

0.151

AC:

779

AN:

5168

South Asian (SAS)

AF:

0.424

AC:

2040

AN:

4812

European-Finnish (FIN)

AF:

0.430

AC:

4543

AN:

10576

Middle Eastern (MID)

AF:

0.361

AC:

106

AN:

294

European-Non Finnish (NFE)

AF:

0.378

AC:

25710

AN:

67936

Other (OTH)

AF:

0.355

AC:

748

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1796

3593

5389

7186

8982

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

552

1104

1656

2208

2760

<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:

0.371

Hom.:

32841

Bravo

AF:

0.374

Asia WGS

AF:

0.337

AC:

1169

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

8.3

(source)

DANN

Benign

0.33

PhyloP100

0.21

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over