3-46578283-G-A

Position:

• chr3-46578283-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003212.4(CRIPTO):​c.35+279G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0357 in 149,466 control chromosomes in the GnomAD database, including 214 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.036 (214 hom., cov: 32)
• Consequence: CRIPTO NM_003212.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.36

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]

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]

TDGF1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 3-46578283-G-A is Benign according to our data. Variant chr3-46578283-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1317567.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.15 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRIPTO	NM_003212.4	c.35+279G>A		intron_variant		ENST00000296145.6	NP_003203.1
CRIPTO	NM_001174136.2	c.-13-812G>A		intron_variant			NP_001167607.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TDGF1	ENST00000296145.6	c.35+279G>A		intron_variant		1	NM_003212.4	ENSP00000296145.5

Frequencies

GnomAD3 genomes AF: 0.0357 AC: 5337 AN: 149348 Hom.: 213 Cov.: 32

Gnomad AFR AF: 0.0100

Gnomad AMI AF: 0.0714

Gnomad AMR AF: 0.0528

Gnomad ASJ AF: 0.0341

Gnomad EAS AF: 0.160

Gnomad SAS AF: 0.151

Gnomad FIN AF: 0.0410

Gnomad MID AF: 0.0909

Gnomad NFE AF: 0.0283

Gnomad OTH AF: 0.0417

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0357 AC: 5339 AN: 149466 Hom.: 214 Cov.: 32 AF XY: 0.0395 AC XY: 2869 AN XY: 72708

Gnomad4 AFR AF: 0.0100

Gnomad4 AMR AF: 0.0527

Gnomad4 ASJ AF: 0.0341

Gnomad4 EAS AF: 0.160

Gnomad4 SAS AF: 0.152

Gnomad4 FIN AF: 0.0410

Gnomad4 NFE AF: 0.0283

Gnomad4 OTH AF: 0.0422

Alfa AF: 0.0288 Hom.: 21

Bravo AF: 0.0335

Asia WGS AF: 0.127 AC: 442 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely 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	-0.89
CADD	Benign	0.065
DANN	Benign	0.32

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs56197743; hg19: chr3-46619773;