Variant chr3-46579311-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_003212.4(CRIPTO):c.168G>A(p.Glu56Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0403 in 1,614,116 control chromosomes in the GnomAD database, including 2,509 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.035 ( 212 hom., cov: 32)

Exomes 𝑓: 0.041 ( 2297 hom. )

Consequence

CRIPTO
NM_003212.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0980

Variant links:

Genes affected

CRIPTO (HGNC:11701): (cripto, EGF-CFC family member) This gene encodes an epidermal growth factor-related protein that contains a cripto, FRL-1, and cryptic domain. The encoded protein is an extracellular, membrane-bound signaling protein that plays an essential role in embryonic development and tumor growth. Mutations in this gene are associated with forebrain defects. Pseudogenes of this gene are found on chromosomes 2, 3, 6, 8, 19 and X. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Mar 2010]

CRIPTO links:

LRRC2 (HGNC:14676): (leucine rich repeat containing 2) This gene encodes a member of the leucine-rich repeat-containing family of proteins, which function in diverse biological pathways. This family member may possibly be a nuclear protein. Similarity to the RAS suppressor protein, as well as expression down-regulation observed in tumor cells, suggests that it may function as a tumor suppressor. The gene is located in the chromosome 3 common eliminated region 1 (C3CER1), a 1.4 Mb region that is commonly deleted in diverse tumors. A related pseudogene has been identified on chromosome 2. [provided by RefSeq, Sep 2011]

LRRC2 links:

TDGF1 (HGNC:):

TDGF1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 3-46579311-G-A is Benign according to our data. Variant chr3-46579311-G-A is described in ClinVar as [Benign]. Clinvar id is 1231198.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.098 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRIPTO	NM_003212.4 linkuse as main transcript	c.168G>A	p.Glu56Glu	synonymous_variant	3/6	ENST00000296145.6	NP_003203.1	P13385
CRIPTO	NM_001174136.2 linkuse as main transcript	c.120G>A	p.Glu40Glu	synonymous_variant	3/6		NP_001167607.1	P13385F5H1T8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TDGF1	ENST00000296145.6 linkuse as main transcript	c.168G>A	p.Glu56Glu	synonymous_variant	3/6	1	NM_003212.4	ENSP00000296145.5		P13385

Frequencies

GnomAD3 genomes

AF:

0.0352

AC:

5359

AN:

152154

Hom.:

211

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00985

Gnomad AMI

AF:

0.0713

Gnomad AMR

AF:

0.0519

Gnomad ASJ

AF:

0.0340

Gnomad EAS

AF:

0.157

Gnomad SAS

AF:

0.147

Gnomad FIN

AF:

0.0387

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.0283

Gnomad OTH

AF:

0.0411

GnomAD3 exomes

AF:

0.0573

AC:

14410

AN:

251456

Hom.:

728

AF XY:

0.0613

AC XY:

8335

AN XY:

135902

show subpopulations

Gnomad AFR exome

AF:

0.00935

Gnomad AMR exome

AF:

0.0537

Gnomad ASJ exome

AF:

0.0340

Gnomad EAS exome

AF:

0.164

Gnomad SAS exome

AF:

0.144

Gnomad FIN exome

AF:

0.0392

Gnomad NFE exome

AF:

0.0306

Gnomad OTH exome

AF:

0.0494

GnomAD4 exome

AF:

0.0408

AC:

59665

AN:

1461844

Hom.:

2297

Cov.:

AF XY:

0.0444

AC XY:

32267

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.00878

Gnomad4 AMR exome

AF:

0.0558

Gnomad4 ASJ exome

AF:

0.0325

Gnomad4 EAS exome

AF:

0.166

Gnomad4 SAS exome

AF:

0.143

Gnomad4 FIN exome

AF:

0.0392

Gnomad4 NFE exome

AF:

0.0285

Gnomad4 OTH exome

AF:

0.0468

GnomAD4 genome

AF:

0.0352

AC:

5361

AN:

152272

Hom.:

212

Cov.:

AF XY:

0.0388

AC XY:

2887

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.00982

Gnomad4 AMR

AF:

0.0518

Gnomad4 ASJ

AF:

0.0340

Gnomad4 EAS

AF:

0.157

Gnomad4 SAS

AF:

0.149

Gnomad4 FIN

AF:

0.0387

Gnomad4 NFE

AF:

0.0283

Gnomad4 OTH

AF:

0.0416

Alfa

AF:

0.0283

Hom.:

Bravo

AF:

0.0335

Asia WGS

AF:

0.128

AC:

443

AN:

3478

EpiCase

AF:

0.0353

EpiControl

AF:

0.0339

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 29, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

2.2

DANN

Benign

0.82

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