5-133685899-T-C

Variant names:

• chr5-133685899-T-C
• rs4958144
• XM_011543283.2:c.-10-81906A>G

Variant summary

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

The XM_011543283.2(FSTL4):​c.-10-81906A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.452 in 152,040 control chromosomes in the GnomAD database, including 15,802 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 0.45 (15802 hom., cov: 33)
• Consequence: FSTL4 XM_011543283.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.797
• Publications: 2 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=-0.73).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.555 is higher than 0.05.

Variant Effect in Transcripts

 

RefSeq Transcripts

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

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes AF: 0.452 AC: 68656 AN: 151922 Hom.: 15771 Cov.: 33

Gnomad AFR AF: 0.527

Gnomad AMI AF: 0.475

Gnomad AMR AF: 0.455

Gnomad ASJ AF: 0.313

Gnomad EAS AF: 0.573

Gnomad SAS AF: 0.369

Gnomad FIN AF: 0.464

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.443

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

GnomAD4 genome AF: 0.452 AC: 68729 AN: 152040 Hom.: 15802 Cov.: 33 AF XY: 0.454 AC XY: 33743 AN XY: 74322

African (AFR) AF: 0.527 AC: 21865 AN: 41464

American (AMR) AF: 0.456 AC: 6963 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.313 AC: 1087 AN: 3468

East Asian (EAS) AF: 0.573 AC: 2959 AN: 5168

South Asian (SAS) AF: 0.368 AC: 1774 AN: 4818

European-Finnish (FIN) AF: 0.464 AC: 4905 AN: 10564

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.408 AC: 27706 AN: 67960

Other (OTH) AF: 0.439 AC: 928 AN: 2112

Alfa AF: 0.409 Hom.: 21750

Bravo AF: 0.455

Asia WGS AF: 0.440 AC: 1528 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	14
DANN	Benign	0.51
PhyloP100		0.80

Splicing

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

Other links and lift over

dbSNP: rs4958144; hg19: chr5-133021590; COSMIC: COSV107163580;