17-68452981-G-A

Position:

• chr17-68452981-G-A

Variant summary

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

The NM_017983.7(WIPI1):​c.92C>T​(p.Thr31Ile) variant causes a missense change. The variant allele was found at a frequency of 0.765 in 1,611,838 control chromosomes in the GnomAD database, including 473,991 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.78 (46068 hom., cov: 31)
  • Exomes 𝑓: 0.76 (427923 hom.)
• Consequence: WIPI1 NM_017983.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.41

Genes affected

WIPI1 (HGNC:25471): (WD repeat domain, phosphoinositide interacting 1) This gene encodes a WD40 repeat protein. Members of the WD40 repeat family are key components of many essential biologic functions. They regulate the assembly of multiprotein complexes by presenting a beta-propeller platform for simultaneous and reversible protein-protein interactions. Members of the WIPI subfamily of WD40 repeat proteins have a 7-bladed propeller structure and contain a conserved motif for interaction with phospholipids. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.61811E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.837 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WIPI1	NM_017983.7	c.92C>T	p.Thr31Ile	missense_variant	2/13	ENST00000262139.10	NP_060453.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WIPI1	ENST00000262139.10	c.92C>T	p.Thr31Ile	missense_variant	2/13	1	NM_017983.7	ENSP00000262139	P1
	ENST00000590353.1	n.173+39186G>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.775 AC: 117822 AN: 151970 Hom.: 46017 Cov.: 31

Gnomad AFR AF: 0.844

Gnomad AMI AF: 0.655

Gnomad AMR AF: 0.701

Gnomad ASJ AF: 0.772

Gnomad EAS AF: 0.538

Gnomad SAS AF: 0.780

Gnomad FIN AF: 0.748

Gnomad MID AF: 0.797

Gnomad NFE AF: 0.774

Gnomad OTH AF: 0.762

GnomAD3 exomes AF: 0.738 AC: 185431 AN: 251262 Hom.: 69573 AF XY: 0.744 AC XY: 101094 AN XY: 135840

Gnomad AFR exome AF: 0.846

Gnomad AMR exome AF: 0.625

Gnomad ASJ exome AF: 0.770

Gnomad EAS exome AF: 0.515

Gnomad SAS exome AF: 0.783

Gnomad FIN exome AF: 0.756

Gnomad NFE exome AF: 0.774

Gnomad OTH exome AF: 0.752

GnomAD4 exome AF: 0.764 AC: 1114762 AN: 1459750 Hom.: 427923 Cov.: 38 AF XY: 0.764 AC XY: 555177 AN XY: 726288

Gnomad4 AFR exome AF: 0.851

Gnomad4 AMR exome AF: 0.639

Gnomad4 ASJ exome AF: 0.771

Gnomad4 EAS exome AF: 0.548

Gnomad4 SAS exome AF: 0.775

Gnomad4 FIN exome AF: 0.758

Gnomad4 NFE exome AF: 0.773

Gnomad4 OTH exome AF: 0.759

GnomAD4 genome AF: 0.775 AC: 117926 AN: 152088 Hom.: 46068 Cov.: 31 AF XY: 0.771 AC XY: 57318 AN XY: 74356

Gnomad4 AFR AF: 0.844

Gnomad4 AMR AF: 0.701

Gnomad4 ASJ AF: 0.772

Gnomad4 EAS AF: 0.537

Gnomad4 SAS AF: 0.780

Gnomad4 FIN AF: 0.748

Gnomad4 NFE AF: 0.774

Gnomad4 OTH AF: 0.761

Alfa AF: 0.767 Hom.: 114403

Bravo AF: 0.773

TwinsUK AF: 0.770 AC: 2856

ALSPAC AF: 0.766 AC: 2953

ESP6500AA AF: 0.828 AC: 3648

ESP6500EA AF: 0.770 AC: 6620

ExAC AF: 0.747 AC: 90657

Asia WGS AF: 0.662 AC: 2304 AN: 3478

EpiCase AF: 0.773

EpiControl AF: 0.773

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.055
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	18
DANN	Benign	0.94
DEOGEN2	Benign	0.017	T
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.34
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.61	T
MetaRNN	Benign	0.0000026	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-2.1	N
MutationTaster	Benign	1.0	P;P
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	3.1	N
REVEL	Benign	0.12
Sift	Benign	0.23	T
Sift4G	Benign	0.21	T
Polyphen		0.0	B
Vest4		0.094
MPC		0.42
ClinPred		0.023	T
GERP RS		5.0
Varity_R		0.039
gMVP		0.090

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs883541; hg19: chr17-66449122; COSMIC: COSV50929487; COSMIC: COSV50929487;