Variant 3-46578042-C-T 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.35+38C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00689 in 1,607,368 control chromosomes in the GnomAD database, including 680 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.037 ( 360 hom., cov: 33)

Exomes 𝑓: 0.0037 ( 320 hom. )

Consequence

CRIPTO
NM_003212.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.14

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=-0.8).

BP6

Variant 3-46578042-C-T is Benign according to our data. Variant chr3-46578042-C-T is described in ClinVar as [Benign]. Clinvar id is 1233338.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.127 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.35+38C>T		intron_variant		ENST00000296145.6	NP_003203.1	P13385
CRIPTO	NM_001174136.2 linkuse as main transcript	c.-13-1053C>T		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.35+38C>T		intron_variant		1	NM_003212.4	ENSP00000296145.5		P13385

Frequencies

GnomAD3 genomes

AF:

0.0374

AC:

5685

AN:

152008

Hom.:

361

Cov.:

show subpopulations

Gnomad AFR

AF:

0.131

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0133

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000265

Gnomad OTH

AF:

0.0235

GnomAD3 exomes

AF:

0.00990

AC:

2487

AN:

251120

Hom.:

156

AF XY:

0.00729

AC XY:

989

AN XY:

135758

show subpopulations

Gnomad AFR exome

AF:

0.135

Gnomad AMR exome

AF:

0.00657

Gnomad ASJ exome

AF:

0.0000994

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000282

Gnomad OTH exome

AF:

0.00587

GnomAD4 exome

AF:

0.00371

AC:

5394

AN:

1455242

Hom.:

320

Cov.:

AF XY:

0.00326

AC XY:

2361

AN XY:

724360

show subpopulations

Gnomad4 AFR exome

AF:

0.131

Gnomad4 AMR exome

AF:

0.00727

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000174

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000148

Gnomad4 OTH exome

AF:

0.00849

GnomAD4 genome

AF:

0.0374

AC:

5682

AN:

152126

Hom.:

360

Cov.:

AF XY:

0.0364

AC XY:

2707

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.130

Gnomad4 AMR

AF:

0.0132

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000265

Gnomad4 OTH

AF:

0.0232

Alfa

AF:

0.00488

Hom.:

Bravo

AF:

0.0433

Asia WGS

AF:

0.00635

AC:

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

Feb 02, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

7.5

DANN

Benign

0.65

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