rs10515462

Variant names:

• chr5-133746975-T-G
• rs10515462
• XM_011543283.2:c.-11+94977A>C

Variant summary

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

The XM_011543283.2(FSTL4):​c.-11+94977A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0897 in 152,276 control chromosomes in the GnomAD database, including 863 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 0.090 (863 hom., cov: 32)
• Consequence: FSTL4 XM_011543283.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07
• Publications: 0 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.153 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FSTL4	XM_011543283.2	c.-11+94977A>C		intron_variant	Intron 1 of 15		XP_011541585.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.0897 AC: 13652 AN: 152158 Hom.: 861 Cov.: 32

Gnomad AFR AF: 0.0258

Gnomad AMI AF: 0.167

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.0942

Gnomad EAS AF: 0.0658

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0947

Gnomad OTH AF: 0.0977

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

GnomAD4 genome AF: 0.0897 AC: 13659 AN: 152276 Hom.: 863 Cov.: 32 AF XY: 0.0957 AC XY: 7128 AN XY: 74458

African (AFR) AF: 0.0259 AC: 1075 AN: 41560

American (AMR) AF: 0.159 AC: 2429 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0942 AC: 327 AN: 3470

East Asian (EAS) AF: 0.0665 AC: 344 AN: 5172

South Asian (SAS) AF: 0.118 AC: 568 AN: 4826

European-Finnish (FIN) AF: 0.198 AC: 2108 AN: 10622

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0946 AC: 6434 AN: 68008

Other (OTH) AF: 0.0957 AC: 202 AN: 2110

Alfa AF: 0.0967 Hom.: 1068

Bravo AF: 0.0859

Asia WGS AF: 0.0970 AC: 337 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.18
DANN	Benign	0.74
PhyloP100		-1.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10515462; hg19: chr5-133082666;