4-161612253-T-C

Variant names:

• chr4-161612253-T-C
• rs6816684
• NM_020116.5:c.895-24678A>G

Variant summary

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

The NM_020116.5(FSTL5):​c.895-24678A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 152,152 control chromosomes in the GnomAD database, including 6,314 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 0.27 (6314 hom., cov: 33)
• Consequence: FSTL5 NM_020116.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.709
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.533 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FSTL5	NM_020116.5	c.895-24678A>G		intron_variant	Intron 7 of 15	ENST00000306100.10	NP_064501.2
FSTL5	NM_001128427.3	c.892-24678A>G		intron_variant	Intron 7 of 15		NP_001121899.1
FSTL5	NM_001128428.3	c.892-24678A>G		intron_variant	Intron 7 of 14		NP_001121900.1
FSTL5	XM_011532126.1	c.895-24678A>G		intron_variant	Intron 7 of 14		XP_011530428.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FSTL5	ENST00000306100.10	c.895-24678A>G		intron_variant	Intron 7 of 15	1	NM_020116.5	ENSP00000305334.4
FSTL5	ENST00000379164.8	c.892-24678A>G		intron_variant	Intron 7 of 15	1		ENSP00000368462.4
FSTL5	ENST00000427802.2	c.892-24678A>G		intron_variant	Intron 7 of 14	1		ENSP00000389270.2
FSTL5	ENST00000511170.1	n.257-24678A>G		intron_variant	Intron 2 of 4	4

Frequencies

GnomAD3 genomes AF: 0.268 AC: 40728 AN: 152034 Hom.: 6302 Cov.: 33

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.322

Gnomad AMR AF: 0.358

Gnomad ASJ AF: 0.284

Gnomad EAS AF: 0.550

Gnomad SAS AF: 0.376

Gnomad FIN AF: 0.323

Gnomad MID AF: 0.280

Gnomad NFE AF: 0.302

Gnomad OTH AF: 0.289

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

GnomAD4 genome AF: 0.268 AC: 40755 AN: 152152 Hom.: 6314 Cov.: 33 AF XY: 0.276 AC XY: 20497 AN XY: 74380

African (AFR) AF: 0.112 AC: 4664 AN: 41530

American (AMR) AF: 0.359 AC: 5485 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.284 AC: 987 AN: 3470

East Asian (EAS) AF: 0.550 AC: 2841 AN: 5170

South Asian (SAS) AF: 0.376 AC: 1812 AN: 4822

European-Finnish (FIN) AF: 0.323 AC: 3413 AN: 10568

Middle Eastern (MID) AF: 0.281 AC: 82 AN: 292

European-Non Finnish (NFE) AF: 0.302 AC: 20554 AN: 67990

Other (OTH) AF: 0.295 AC: 624 AN: 2116

Alfa AF: 0.299 Hom.: 2718

Bravo AF: 0.265

Asia WGS AF: 0.404 AC: 1405 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.5
DANN	Benign	0.93
PhyloP100		0.71
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6816684; hg19: chr4-162533405;