Genetic Variant CRIPT:n.608+85G>T (chr2-46617108-G-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000486447.1(CRIPT):n.608+85G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 843,824 control chromosomes in the GnomAD database, including 7,845 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 3290 hom., cov: 32)

Exomes 𝑓: 0.099 ( 4555 hom. )

Consequence

CRIPT
ENST00000486447.1 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0690

Variant links:

Genes affected

CRIPT (HGNC:14312): (CXXC repeat containing interactor of PDZ3 domain) This gene encodes a protein that binds to the PDZ3 peptide recognition domain. The encoded protein may modulates protein interactions with the cytoskeleton. A mutation in this gene resulted in short stature with microcephaly and distinctive facies. [provided by RefSeq, Jun 2014]

CRIPT links:

PIGF (HGNC:8962): (phosphatidylinositol glycan anchor biosynthesis class F) This gene encodes a protein involved in glycosylphosphatidylinositol (GPI)-anchor biosynthesis. The GPI-anchor, a glycolipid containing three mannose molecules in its core backbone, is found on many blood cells where it serves to anchor proteins to the cell surface. The encoded protein and another GPI synthesis protein, PIGO, function in the transfer of ethanolaminephosphate to the third mannose in GPI. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

PIGF links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 2-46617108-G-T is Benign according to our data. Variant chr2-46617108-G-T is described in ClinVar as [Benign]. Clinvar id is 1251822.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.36 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIGF	NM_002643.4 link	c.-160C>A		upstream_gene_variant		ENST00000281382.11	NP_002634.1	Q07326-1Q6IB04
CRIPT	NM_014171.6 link	c.-175G>T		upstream_gene_variant		ENST00000238892.4	NP_054890.1	Q9P021

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIGF	ENST00000281382.11 link	c.-160C>A		upstream_gene_variant		1	NM_002643.4	ENSP00000281382.6		Q07326-1
CRIPT	ENST00000238892.4 link	c.-175G>T		upstream_gene_variant		1	NM_014171.6	ENSP00000238892.3		Q9P021

Frequencies

GnomAD3 genomes

AF:

0.163

AC:

24805

AN:

152086

Hom.:

3279

Cov.:

show subpopulations

Gnomad AFR

AF:

0.365

Gnomad AMI

AF:

0.0504

Gnomad AMR

AF:

0.112

Gnomad ASJ

AF:

0.101

Gnomad EAS

AF:

0.0392

Gnomad SAS

AF:

0.150

Gnomad FIN

AF:

0.0468

Gnomad MID

AF:

0.149

Gnomad NFE

AF:

0.0858

Gnomad OTH

AF:

0.133

GnomAD4 exome

AF:

0.0992

AC:

68623

AN:

691620

Hom.:

4555

Cov.:

AF XY:

0.0998

AC XY:

36189

AN XY:

362546

show subpopulations

Gnomad4 AFR exome

AF:

0.374

Gnomad4 AMR exome

AF:

0.0997

Gnomad4 ASJ exome

AF:

0.104

Gnomad4 EAS exome

AF:

0.0467

Gnomad4 SAS exome

AF:

0.144

Gnomad4 FIN exome

AF:

0.0553

Gnomad4 NFE exome

AF:

0.0880

Gnomad4 OTH exome

AF:

0.106

GnomAD4 genome

AF:

0.163

AC:

24849

AN:

152204

Hom.:

3290

Cov.:

AF XY:

0.158

AC XY:

11725

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.365

Gnomad4 AMR

AF:

0.112

Gnomad4 ASJ

AF:

0.101

Gnomad4 EAS

AF:

0.0393

Gnomad4 SAS

AF:

0.149

Gnomad4 FIN

AF:

0.0468

Gnomad4 NFE

AF:

0.0858

Gnomad4 OTH

AF:

0.133

Alfa

AF:

0.0891

Hom.:

225

Bravo

AF:

0.177

Asia WGS

AF:

0.111

AC:

388

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

7.8

DANN

Benign

0.91

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over