4-161901154-T-G

Variant summary

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

The NM_020116.5(FSTL5):c.409+19250A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.824 in 151,462 control chromosomes in the GnomAD database, including 52,127 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 0.82 (52127 hom., cov: 30)
• Consequence: FSTL5 NM_020116.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.21

Genes affected

FSTL5 (HGNC:21386): (follistatin like 5) Predicted to enable calcium ion binding activity. Predicted to be involved in cell differentiation. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.887 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FSTL5	NM_020116.5	c.409+19250A>C		intron_variant		ENST00000306100.10
FSTL5	NM_001128427.3	c.406+19250A>C		intron_variant
FSTL5	NM_001128428.3	c.406+19250A>C		intron_variant
FSTL5	XM_011532126.1	c.409+19250A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FSTL5	ENST00000306100.10	c.409+19250A>C		intron_variant		1	NM_020116.5	P5
FSTL5	ENST00000379164.8	c.406+19250A>C		intron_variant		1		A1
FSTL5	ENST00000427802.2	c.406+19250A>C		intron_variant		1		A1

Frequencies

GnomAD3 genomes AF: 0.824 AC: 124771 AN: 151360 Hom.: 52107 Cov.: 30

Gnomad AFR AF: 0.671

Gnomad AMI AF: 0.934

Gnomad AMR AF: 0.856

Gnomad ASJ AF: 0.933

Gnomad EAS AF: 0.813

Gnomad SAS AF: 0.823

Gnomad FIN AF: 0.892

Gnomad MID AF: 0.865

Gnomad NFE AF: 0.893

Gnomad OTH AF: 0.841

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

GnomAD4 genome AF: 0.824 AC: 124830 AN: 151462 Hom.: 52127 Cov.: 30 AF XY: 0.825 AC XY: 61042 AN XY: 73974

Gnomad4 AFR AF: 0.671

Gnomad4 AMR AF: 0.856

Gnomad4 ASJ AF: 0.933

Gnomad4 EAS AF: 0.813

Gnomad4 SAS AF: 0.824

Gnomad4 FIN AF: 0.892

Gnomad4 NFE AF: 0.893

Gnomad4 OTH AF: 0.842

Alfa AF: 0.875 Hom.: 26687

Bravo AF: 0.815

Asia WGS AF: 0.807 AC: 2804 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	0.15
Dann	Benign	0.52

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: rs2033404; hg19: chr4-162822306;