rs17763463

Positions:

• chr2-24033201-T-C

Variant summary

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

The NM_025203.3(WDCP):​c.1819-255A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0908 in 568,198 control chromosomes in the GnomAD database, including 2,704 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 0.081 (570 hom., cov: 32)
  • Exomes 𝑓: 0.095 (2134 hom.)
• Consequence: WDCP NM_025203.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.398

Genes affected

WDCP (HGNC:26157): (WD repeat and coiled coil containing) Enables kinase binding activity. Involved in protein complex oligomerization. [provided by Alliance of Genome Resources, Apr 2022]

MFSD2B (HGNC:37207): (MFSD2 lysolipid transporter B, sphingolipid) Enables sphingolipid transporter activity. Involved in lipid transport. Is integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

FKBP1B (HGNC:3712): (FKBP prolyl isomerase 1B) 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 the immunosuppressants FK506 and rapamycin. It is highly similar to the FK506-binding protein 1A. Its physiological role is thought to be in excitation-contraction coupling in cardiac muscle. There are two alternatively spliced transcript variants of this gene encoding different isoforms. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDCP	NM_025203.3	c.1819-255A>G		intron_variant		ENST00000295148.9	NP_079479.1
WDCP	NM_001142319.2	c.1819-2039A>G		intron_variant			NP_001135791.1
FKBP1B	XM_017003594.2	c.-107T>C		upstream_gene_variant			XP_016859083.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDCP	ENST00000295148.9	c.1819-255A>G		intron_variant		2	NM_025203.3	ENSP00000295148.4
WDCP	ENST00000406895.3	c.1819-2039A>G		intron_variant		1		ENSP00000385816.3
MFSD2B	ENST00000453731.1	n.*19T>C		non_coding_transcript_exon_variant	2/5	3		ENSP00000390490.1
MFSD2B	ENST00000453731.1	n.*19T>C		3_prime_UTR_variant	2/5	3		ENSP00000390490.1

Frequencies

GnomAD3 genomes AF: 0.0806 AC: 12254 AN: 152062 Hom.: 572 Cov.: 32

Gnomad AFR AF: 0.0552

Gnomad AMI AF: 0.180

Gnomad AMR AF: 0.0778

Gnomad ASJ AF: 0.0772

Gnomad EAS AF: 0.0148

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.0620

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0982

Gnomad OTH AF: 0.0894

GnomAD3 exomes AF: 0.0851 AC: 12444 AN: 146236 Hom.: 672 AF XY: 0.0919 AC XY: 7246 AN XY: 78840

Gnomad AFR exome AF: 0.0539

Gnomad AMR exome AF: 0.0477

Gnomad ASJ exome AF: 0.0770

Gnomad EAS exome AF: 0.0121

Gnomad SAS exome AF: 0.146

Gnomad FIN exome AF: 0.0666

Gnomad NFE exome AF: 0.100

Gnomad OTH exome AF: 0.103

GnomAD4 exome AF: 0.0946 AC: 39346 AN: 416018 Hom.: 2134 Cov.: 0 AF XY: 0.100 AC XY: 22938 AN XY: 229378

Gnomad4 AFR exome AF: 0.0519

Gnomad4 AMR exome AF: 0.0500

Gnomad4 ASJ exome AF: 0.0790

Gnomad4 EAS exome AF: 0.0228

Gnomad4 SAS exome AF: 0.147

Gnomad4 FIN exome AF: 0.0675

Gnomad4 NFE exome AF: 0.0995

Gnomad4 OTH exome AF: 0.0877

GnomAD4 genome AF: 0.0806 AC: 12259 AN: 152180 Hom.: 570 Cov.: 32 AF XY: 0.0801 AC XY: 5957 AN XY: 74404

Gnomad4 AFR AF: 0.0552

Gnomad4 AMR AF: 0.0777

Gnomad4 ASJ AF: 0.0772

Gnomad4 EAS AF: 0.0151

Gnomad4 SAS AF: 0.148

Gnomad4 FIN AF: 0.0620

Gnomad4 NFE AF: 0.0983

Gnomad4 OTH AF: 0.0889

Alfa AF: 0.0957 Hom.: 1008

Bravo AF: 0.0785

Asia WGS AF: 0.0810 AC: 281 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.6
DANN	Benign	0.73
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs17763463; hg19: chr2-24256071;