Genetic Variant NM_020116.5:c.1842-533C>G (chr4-161386982-G-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_020116.5(FSTL5):c.1842-533C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0399 in 153,954 control chromosomes in the GnomAD database, including 326 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 0.040 ( 320 hom., cov: 33)

Exomes 𝑓: 0.057 ( 6 hom. )

Consequence

FSTL5
NM_020116.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.126

Publications

3 publications found

Variant links:

Genes affected

FSTL5 (HGNC:21386): (follistatin like 5) Predicted to enable calcium ion binding activity. Predicted to be involved in cell differentiation. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

FSTL5 links:

ENSG00000249568 (HGNC:):

ENSG00000249568 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=-0.92).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.171 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
FSTL5	NM_020116.5 link	c.1842-533C>G	intron_variant	Intron 15 of 15	ENST00000306100.10	NP_064501.2	Q8N475-1
FSTL5	NM_001128427.3 link	c.1839-533C>G	intron_variant	Intron 15 of 15		NP_001121899.1	Q8N475-2
FSTL5	NM_001128428.3 link	c.1812-533C>G	intron_variant	Intron 14 of 14		NP_001121900.1	Q8N475-3
FSTL5	XM_011532126.1 link	c.1815-533C>G	intron_variant	Intron 14 of 14		XP_011530428.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
FSTL5	ENST00000306100.10 link	c.1842-533C>G	intron_variant	Intron 15 of 15	1	NM_020116.5	ENSP00000305334.4	Q8N475-1
FSTL5	ENST00000379164.8 link	c.1839-533C>G	intron_variant	Intron 15 of 15	1		ENSP00000368462.4	Q8N475-2
FSTL5	ENST00000427802.2 link	c.1812-533C>G	intron_variant	Intron 14 of 14	1		ENSP00000389270.2	Q8N475-3
ENSG00000249568	ENST00000508189.1 link	n.1405G>C	non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.0395

AC:

5998

AN:

151758

Hom.:

312

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00542

Gnomad AMI

AF:

0.0538

Gnomad AMR

AF:

0.114

Gnomad ASJ

AF:

0.0337

Gnomad EAS

AF:

0.180

Gnomad SAS

AF:

0.157

Gnomad FIN

AF:

0.0370

Gnomad MID

AF:

0.0128

Gnomad NFE

AF:

0.0251

Gnomad OTH

AF:

0.0458

GnomAD4 exome

AF:

0.0568

AC:

118

AN:

2078

Hom.:

Cov.:

AF XY:

0.0578

AC XY:

AN XY:

1090

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.148

AC:

AN:

420

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.143

AC:

AN:

South Asian (SAS)

AF:

0.137

AC:

AN:

190

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0188

AC:

AN:

1384

Other (OTH)

AF:

0.0313

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.0397

AC:

6026

AN:

151876

Hom.:

320

Cov.:

AF XY:

0.0444

AC XY:

3293

AN XY:

74238

show subpopulations

African (AFR)

AF:

0.00540

AC:

224

AN:

41470

American (AMR)

AF:

0.114

AC:

1745

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.0337

AC:

117

AN:

3468

East Asian (EAS)

AF:

0.180

AC:

928

AN:

5152

South Asian (SAS)

AF:

0.157

AC:

754

AN:

4810

European-Finnish (FIN)

AF:

0.0370

AC:

390

AN:

10536

Middle Eastern (MID)

AF:

0.00690

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.0251

AC:

1705

AN:

67892

Other (OTH)

AF:

0.0534

AC:

112

AN:

2096

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

274

548

823

1097

1371

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

168

252

336

420

<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:

0.0388

Hom.:

Bravo

AF:

0.0414

Asia WGS

AF:

0.193

AC:

663

AN:

3446

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.37

(source)

DANN

Benign

0.57

PhyloP100

-0.13

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