Genetic Variant NM_015082.2:c.*1270T>G (chr5-133197825-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_015082.2(FSTL4):c.*1270T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 152,142 control chromosomes in the GnomAD database, including 6,477 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 0.28 ( 6471 hom., cov: 32)

Exomes 𝑓: 0.29 ( 6 hom. )

Consequence

FSTL4
NM_015082.2 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.47

Publications

13 publications found

Variant links:

Genes affected

FSTL4 (HGNC:21389): (follistatin like 4) Predicted to enable brain-derived neurotrophic factor binding activity and calcium ion binding activity. Predicted to be involved in cell differentiation. Predicted to act upstream of or within negative regulation of brain-derived neurotrophic factor receptor signaling pathway; negative regulation of collateral sprouting; and negative regulation of dendritic spine development. Predicted to be located in extracellular region and secretory granule. [provided by Alliance of Genome Resources, Apr 2022]

FSTL4 links:

ENSG00000248245 (HGNC:):

ENSG00000248245 links:

Genome browser will be placed here

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=-0.9).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.426 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FSTL4	NM_015082.2 link	c.*1270T>G		3_prime_UTR_variant	Exon 16 of 16	ENST00000265342.12	NP_055897.1	Q6MZW2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FSTL4	ENST00000265342.12 link	c.*1270T>G		3_prime_UTR_variant	Exon 16 of 16	5	NM_015082.2	ENSP00000265342.7		Q6MZW2-1
ENSG00000248245	ENST00000509051.1 link	n.76-10011A>C		intron_variant	Intron 1 of 3	4

Frequencies

GnomAD3 genomes

AF:

0.282

AC:

42916

AN:

151924

Hom.:

6455

Cov.:

show subpopulations

Gnomad AFR

AF:

0.245

Gnomad AMI

AF:

0.308

Gnomad AMR

AF:

0.370

Gnomad ASJ

AF:

0.322

Gnomad EAS

AF:

0.442

Gnomad SAS

AF:

0.386

Gnomad FIN

AF:

0.419

Gnomad MID

AF:

0.256

Gnomad NFE

AF:

0.243

Gnomad OTH

AF:

0.287

GnomAD4 exome

AF:

0.290

AC:

AN:

100

Hom.:

Cov.:

AF XY:

0.250

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.417

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.236

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.283

AC:

42970

AN:

152042

Hom.:

6471

Cov.:

AF XY:

0.294

AC XY:

21878

AN XY:

74322

show subpopulations

African (AFR)

AF:

0.245

AC:

10169

AN:

41462

American (AMR)

AF:

0.371

AC:

5674

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.322

AC:

1116

AN:

3470

East Asian (EAS)

AF:

0.441

AC:

2277

AN:

5160

South Asian (SAS)

AF:

0.387

AC:

1865

AN:

4818

European-Finnish (FIN)

AF:

0.419

AC:

4420

AN:

10552

Middle Eastern (MID)

AF:

0.255

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.243

AC:

16494

AN:

67980

Other (OTH)

AF:

0.285

AC:

600

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1545

3090

4636

6181

7726

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

442

884

1326

1768

2210

<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:

0.261

Hom.:

9084

Bravo

AF:

0.282

Asia WGS

AF:

0.385

AC:

1341

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.58

(source)

DANN

Benign

0.45

PhyloP100

-1.5

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