dbSNP rs2817035: LOC285847:n.1226C>T (chr6-35728586-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.05

Publications

13 publications found

Variant links:

Genes affected

LOC285847 (HGNC:):

LOC285847 links:

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]

FKBP5 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
LOC285847	NR_027117.2 link	n.1226C>T		non_coding_transcript_exon_variant	Exon 8 of 10
FKBP5	NM_001145775.3 link	c.-319C>T		upstream_gene_variant			NP_001139247.1	Q13451-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000299371	ENST00000762917.1 link	n.171+736C>T		intron_variant	Intron 2 of 2
FKBP5	ENST00000536438.5 link	c.-319C>T		upstream_gene_variant		1		ENSP00000444810.1		Q13451-1

Frequencies

GnomAD3 genomes

AF:

0.232

AC:

35194

AN:

151910

Hom.:

4661

Cov.:

show subpopulations

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:

AN:

186

Hom.:

Cov.:

AF XY:

0.340

AC XY:

AN XY:

144

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.667

AC:

AN:

South Asian (SAS)

AF:

0.500

AC:

AN:

European-Finnish (FIN)

AF:

0.667

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.253

AC:

AN:

146

Other (OTH)

AF:

0.357

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.232

AC:

35202

AN:

152026

Hom.:

4664

Cov.:

AF XY:

0.234

AC XY:

17404

AN XY:

74310

show subpopulations

African (AFR)

AF:

0.0954

AC:

3958

AN:

41496

American (AMR)

AF:

0.274

AC:

4181

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.277

AC:

961

AN:

3472

East Asian (EAS)

AF:

0.235

AC:

1213

AN:

5164

South Asian (SAS)

AF:

0.368

AC:

1773

AN:

4814

European-Finnish (FIN)

AF:

0.264

AC:

2789

AN:

10556

Middle Eastern (MID)

AF:

0.295

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.285

AC:

19371

AN:

67940

Other (OTH)

AF:

0.248

AC:

522

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1353

2705

4058

5410

6763

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

368

736

1104

1472

1840

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.231

Hom.:

695

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

(source)

DANN

Benign

0.80

PhyloP100

1.1

PromoterAI

0.0034

Neutral

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over