5-133230519-A-G

Variant names:

• chr5-133230519-A-G
• rs959727
• NM_015082.2:c.1015+2898T>C

Variant summary

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

The NM_015082.2(FSTL4):​c.1015+2898T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.48 in 152,080 control chromosomes in the GnomAD database, including 17,838 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 0.48 (17838 hom., cov: 32)
• Consequence: FSTL4 NM_015082.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.262
• Publications: 7 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.698 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FSTL4	NM_015082.2	c.1015+2898T>C		intron_variant	Intron 8 of 15	ENST00000265342.12	NP_055897.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FSTL4	ENST00000265342.12	c.1015+2898T>C		intron_variant	Intron 8 of 15	5	NM_015082.2	ENSP00000265342.7
FSTL4	ENST00000507112.1	n.426+2898T>C		intron_variant	Intron 3 of 5	3

Frequencies

GnomAD3 genomes AF: 0.480 AC: 72891 AN: 151962 Hom.: 17825 Cov.: 32

Gnomad AFR AF: 0.487

Gnomad AMI AF: 0.260

Gnomad AMR AF: 0.520

Gnomad ASJ AF: 0.518

Gnomad EAS AF: 0.717

Gnomad SAS AF: 0.478

Gnomad FIN AF: 0.508

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.445

Gnomad OTH AF: 0.471

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

GnomAD4 genome AF: 0.480 AC: 72940 AN: 152080 Hom.: 17838 Cov.: 32 AF XY: 0.485 AC XY: 36027 AN XY: 74336

African (AFR) AF: 0.487 AC: 20195 AN: 41488

American (AMR) AF: 0.521 AC: 7972 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.518 AC: 1800 AN: 3472

East Asian (EAS) AF: 0.717 AC: 3696 AN: 5154

South Asian (SAS) AF: 0.478 AC: 2303 AN: 4816

European-Finnish (FIN) AF: 0.508 AC: 5369 AN: 10570

Middle Eastern (MID) AF: 0.558 AC: 164 AN: 294

European-Non Finnish (NFE) AF: 0.445 AC: 30216 AN: 67960

Other (OTH) AF: 0.468 AC: 988 AN: 2110

Alfa AF: 0.457 Hom.: 51641

Bravo AF: 0.481

Asia WGS AF: 0.540 AC: 1878 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.8
DANN	Benign	0.57
PhyloP100		-0.26
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs959727; hg19: chr5-132566211;