rs6870951

Variant names:

• chr5-133729269-C-T
• rs6870951
• XM_011543283.2:c.-11+112683G>A

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+112683G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 151,788 control chromosomes in the GnomAD database, including 2,650 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 0.15 (2650 hom., cov: 31)
• Consequence: FSTL4 XM_011543283.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.523
• Publications: 3 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

Variant Effect in Transcripts

 

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23233 AN: 151670 Hom.: 2642 Cov.: 31

Gnomad AFR AF: 0.318

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.0925

Gnomad ASJ AF: 0.0865

Gnomad EAS AF: 0.00790

Gnomad SAS AF: 0.0571

Gnomad FIN AF: 0.0677

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.122

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

GnomAD4 genome AF: 0.153 AC: 23251 AN: 151788 Hom.: 2650 Cov.: 31 AF XY: 0.148 AC XY: 11014 AN XY: 74172

African (AFR) AF: 0.318 AC: 13135 AN: 41340

American (AMR) AF: 0.0924 AC: 1409 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.0865 AC: 300 AN: 3468

East Asian (EAS) AF: 0.00792 AC: 41 AN: 5178

South Asian (SAS) AF: 0.0569 AC: 272 AN: 4780

European-Finnish (FIN) AF: 0.0677 AC: 713 AN: 10526

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.103 AC: 6983 AN: 67932

Other (OTH) AF: 0.120 AC: 253 AN: 2110

Alfa AF: 0.117 Hom.: 4098

Bravo AF: 0.162

Asia WGS AF: 0.0580 AC: 206 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.4
DANN	Benign	0.26
PhyloP100		0.52

Splicing

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

Other links and lift over

dbSNP: rs6870951; hg19: chr5-133064960;