Variant 3-46577270-A-C 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_001174136.2(CRIPTO):c.-13-1825A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.527 in 152,124 control chromosomes in the GnomAD database, including 21,310 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.53 ( 21286 hom., cov: 32)

Exomes 𝑓: 0.46 ( 24 hom. )

Consequence

CRIPTO
NM_001174136.2 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.52

Variant links:

Genes affected

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:

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:

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=-0.95).

BP6

Variant 3-46577270-A-C is Benign according to our data. Variant chr3-46577270-A-C is described in ClinVar as [Benign]. Clinvar id is 1228609.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.579 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRIPTO	NM_001174136.2 linkuse as main transcript	c.-13-1825A>C		intron_variant			NP_001167607.1	P13385F5H1T8

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	Protein	UniProt
LRRC2	ENST00000296144.3 linkuse as main transcript	c.-20+2667T>G	intron_variant	1	ENSP00000296144.3	Q9BYS8
LRRC2	ENST00000682605.1 linkuse as main transcript	c.-19-25660T>G	intron_variant		ENSP00000507018.1	Q9BYS8
TDGF1	ENST00000542931.6 linkuse as main transcript	c.-13-1825A>C	intron_variant	5	ENSP00000446375.1	F5H1T8

Frequencies

GnomAD3 genomes

AF:

0.527

AC:

79998

AN:

151802

Hom.:

21288

Cov.:

show subpopulations

Gnomad AFR

AF:

0.534

Gnomad AMI

AF:

0.526

Gnomad AMR

AF:

0.481

Gnomad ASJ

AF:

0.465

Gnomad EAS

AF:

0.393

Gnomad SAS

AF:

0.597

Gnomad FIN

AF:

0.522

Gnomad MID

AF:

0.646

Gnomad NFE

AF:

0.540

Gnomad OTH

AF:

0.559

GnomAD4 exome

AF:

0.461

AC:

AN:

204

Hom.:

Cov.:

AF XY:

0.453

AC XY:

AN XY:

148

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.500

Gnomad4 ASJ exome

AF:

0.500

Gnomad4 EAS exome

AF:

0.750

Gnomad4 SAS exome

AF:

0.500

Gnomad4 FIN exome

AF:

0.500

Gnomad4 NFE exome

AF:

0.458

Gnomad4 OTH exome

AF:

0.400

GnomAD4 genome

AF:

0.527

AC:

80016

AN:

151920

Hom.:

21286

Cov.:

AF XY:

0.525

AC XY:

38954

AN XY:

74236

show subpopulations

Gnomad4 AFR

AF:

0.533

Gnomad4 AMR

AF:

0.482

Gnomad4 ASJ

AF:

0.465

Gnomad4 EAS

AF:

0.393

Gnomad4 SAS

AF:

0.597

Gnomad4 FIN

AF:

0.522

Gnomad4 NFE

AF:

0.540

Gnomad4 OTH

AF:

0.552

Alfa

AF:

0.477

Hom.:

3209

Bravo

AF:

0.522

Asia WGS

AF:

0.482

AC:

1674

AN:

3476

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

Nov 27, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.065

DANN

Benign

0.40

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