7-73332645-C-T

Position:

• chr7-73332645-C-T

Variant summary

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

The NM_003602.5(FKBP6):​c.588+869C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0327 in 152,152 control chromosomes in the GnomAD database, including 279 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 0.033 (279 hom., cov: 32)
• Consequence: FKBP6 NM_003602.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.882

Genes affected

FKBP6 (HGNC:3722): (FKBP prolyl isomerase family member 6 (inactive)) The protein encoded by this gene is a cis-trans peptidyl-prolyl isomerase that may function in immunoregulation and basic cellular processes involving protein folding and trafficking. This gene is located in a chromosomal region that is deleted in Williams-Beuren syndrome. Defects in this gene may cause male infertility. There are multiple pseudogenes for this gene located nearby on chromosome 7. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FKBP6	NM_003602.5	c.588+869C>T		intron_variant		ENST00000252037.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FKBP6	ENST00000252037.5	c.588+869C>T		intron_variant		1	NM_003602.5	P4

Frequencies

GnomAD3 genomes AF: 0.0326 AC: 4955 AN: 152034 Hom.: 271 Cov.: 32

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0140

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00125

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.000720

Gnomad OTH AF: 0.0230

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

GnomAD4 genome AF: 0.0327 AC: 4979 AN: 152152 Hom.: 279 Cov.: 32 AF XY: 0.0320 AC XY: 2381 AN XY: 74398

Gnomad4 AFR AF: 0.112

Gnomad4 AMR AF: 0.0140

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00125

Gnomad4 FIN AF: 0.0000942

Gnomad4 NFE AF: 0.000720

Gnomad4 OTH AF: 0.0227

Alfa AF: 0.00461 Hom.: 31

Bravo AF: 0.0381

Asia WGS AF: 0.00837 AC: 29 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	4.4
DANN	Benign	0.40

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: rs6943090; hg19: chr7-72746648;