rs2817035

Positions:

• chr6-35728586-G-A

Variant summary

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

The NR_027117.2(LOC285847):​n.1226C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 152,212 control chromosomes in the GnomAD database, including 4,673 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 0.23 (4664 hom., cov: 31)
  • Exomes 𝑓: 0.30 (9 hom.)
• Consequence: LOC285847 NR_027117.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.05

Genes affected

LOC285847 (HGNC:):

FKBP5 (HGNC:3721): (FKBP prolyl isomerase 5) The protein encoded by this gene is a member of the immunophilin protein family, which play a role in immunoregulation and basic cellular processes involving protein folding and trafficking. This encoded protein is a cis-trans prolyl isomerase that binds to the immunosuppressants FK506 and rapamycin. It is thought to mediate calcineurin inhibition. It also interacts functionally with mature hetero-oligomeric progesterone receptor complexes along with the 90 kDa heat shock protein and P23 protein. This gene has been found to have multiple polyadenylation sites. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Mar 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.354 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC285847	NR_027117.2	n.1226C>T		non_coding_transcript_exon_variant	8/10
		n.35728586G>A		intergenic_region
FKBP5	NM_001145775.3	c.-319C>T		upstream_gene_variant			NP_001139247.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FKBP5	ENST00000536438.5	c.-319C>T		upstream_gene_variant		1		ENSP00000444810.1

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35194 AN: 151910 Hom.: 4661 Cov.: 31

Gnomad AFR AF: 0.0955

Gnomad AMI AF: 0.382

Gnomad AMR AF: 0.274

Gnomad ASJ AF: 0.277

Gnomad EAS AF: 0.235

Gnomad SAS AF: 0.369

Gnomad FIN AF: 0.264

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.285

Gnomad OTH AF: 0.244

GnomAD4 exome AF: 0.301 AC: 56 AN: 186 Hom.: 9 Cov.: 0 AF XY: 0.340 AC XY: 49 AN XY: 144

Gnomad4 AFR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.667

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.667

Gnomad4 NFE exome AF: 0.253

Gnomad4 OTH exome AF: 0.357

GnomAD4 genome AF: 0.232 AC: 35202 AN: 152026 Hom.: 4664 Cov.: 31 AF XY: 0.234 AC XY: 17404 AN XY: 74310

Gnomad4 AFR AF: 0.0954

Gnomad4 AMR AF: 0.274

Gnomad4 ASJ AF: 0.277

Gnomad4 EAS AF: 0.235

Gnomad4 SAS AF: 0.368

Gnomad4 FIN AF: 0.264

Gnomad4 NFE AF: 0.285

Gnomad4 OTH AF: 0.248

Alfa AF: 0.236 Hom.: 692

Bravo AF: 0.224

Asia WGS AF: 0.301 AC: 1048 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	5.9
DANN	Benign	0.80

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2817035; hg19: chr6-35696363;