5-133204417-T-C

Position:

• chr5-133204417-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015082.2(FSTL4):​c.1717-2375A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.615 in 152,104 control chromosomes in the GnomAD database, including 29,135 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 0.62 (29135 hom., cov: 33)
• Consequence: FSTL4 NM_015082.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.239

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 = 0.687 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FSTL4	NM_015082.2	c.1717-2375A>G		intron_variant		ENST00000265342.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FSTL4	ENST00000265342.12	c.1717-2375A>G		intron_variant		5	NM_015082.2	P1
	ENST00000509051.1	n.76-3419T>C		intron_variant, non_coding_transcript_variant		4
FSTL4	ENST00000509525.5	n.935-2375A>G		intron_variant, non_coding_transcript_variant		2
FSTL4	ENST00000511375.1	n.105-1676A>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.615 AC: 93487 AN: 151986 Hom.: 29100 Cov.: 33

Gnomad AFR AF: 0.640

Gnomad AMI AF: 0.514

Gnomad AMR AF: 0.697

Gnomad ASJ AF: 0.627

Gnomad EAS AF: 0.646

Gnomad SAS AF: 0.637

Gnomad FIN AF: 0.720

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.561

Gnomad OTH AF: 0.611

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

GnomAD4 genome AF: 0.615 AC: 93580 AN: 152104 Hom.: 29135 Cov.: 33 AF XY: 0.624 AC XY: 46422 AN XY: 74364

Gnomad4 AFR AF: 0.641

Gnomad4 AMR AF: 0.698

Gnomad4 ASJ AF: 0.627

Gnomad4 EAS AF: 0.646

Gnomad4 SAS AF: 0.638

Gnomad4 FIN AF: 0.720

Gnomad4 NFE AF: 0.561

Gnomad4 OTH AF: 0.609

Alfa AF: 0.575 Hom.: 32943

Bravo AF: 0.618

Asia WGS AF: 0.600 AC: 2091 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	1.4
DANN	Benign	0.82

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

LitVar

Other links and lift over

dbSNP: rs2162769; hg19: chr5-132540109; COSMIC: COSV54766599;