Variant 3-46579409-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_003212.4(CRIPTO):c.223+43T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0401 in 1,613,826 control chromosomes in the GnomAD database, including 2,504 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.034 ( 210 hom., cov: 32)

Exomes 𝑓: 0.041 ( 2294 hom. )

Consequence

CRIPTO
NM_003212.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.10

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 3-46579409-T-A is Benign according to our data. Variant chr3-46579409-T-A is described in ClinVar as [Benign]. Clinvar id is 1237964.Status of the report is criteria_provided_single_submitter, 1 stars.

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.223+43T>A		intron_variant		ENST00000296145.6	NP_003203.1	P13385
CRIPTO	NM_001174136.2 linkuse as main transcript	c.175+43T>A		intron_variant			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.223+43T>A		intron_variant		1	NM_003212.4	ENSP00000296145.5		P13385

Frequencies

GnomAD3 genomes

AF:

0.0345

AC:

5249

AN:

152126

Hom.:

209

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00748

Gnomad AMI

AF:

0.0713

Gnomad AMR

AF:

0.0512

Gnomad ASJ

AF:

0.0340

Gnomad EAS

AF:

0.157

Gnomad SAS

AF:

0.148

Gnomad FIN

AF:

0.0387

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.0283

Gnomad OTH

AF:

0.0402

GnomAD3 exomes

AF:

0.0573

AC:

14320

AN:

250030

Hom.:

729

AF XY:

0.0613

AC XY:

8309

AN XY:

135612

show subpopulations

Gnomad AFR exome

AF:

0.00641

Gnomad AMR exome

AF:

0.0536

Gnomad ASJ exome

AF:

0.0340

Gnomad EAS exome

AF:

0.165

Gnomad SAS exome

AF:

0.144

Gnomad FIN exome

AF:

0.0392

Gnomad NFE exome

AF:

0.0305

Gnomad OTH exome

AF:

0.0494

GnomAD4 exome

AF:

0.0407

AC:

59496

AN:

1461582

Hom.:

2294

Cov.:

AF XY:

0.0443

AC XY:

32184

AN XY:

727096

show subpopulations

Gnomad4 AFR exome

AF:

0.00556

Gnomad4 AMR exome

AF:

0.0556

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:

0.0465

GnomAD4 genome

AF:

0.0345

AC:

5251

AN:

152244

Hom.:

210

Cov.:

AF XY:

0.0382

AC XY:

2840

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.00746

Gnomad4 AMR

AF:

0.0511

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:

0.0408

Alfa

AF:

0.0310

Hom.:

Bravo

AF:

0.0325

Asia WGS

AF:

0.128

AC:

443

AN:

3478

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

-0.85

CADD

Benign

0.18

DANN

Benign

0.52

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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