Variant 10-43116778-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_020975.6(RET):c.2284+47C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 1,420,794 control chromosomes in the GnomAD database, including 40,832 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 3404 hom., cov: 31)

Exomes 𝑓: 0.23 ( 37428 hom. )

Consequence

RET
NM_020975.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.973

Variant links:

Genes affected

RET (HGNC:9967): (ret proto-oncogene) This gene encodes a transmembrane receptor and member of the tyrosine protein kinase family of proteins. Binding of ligands such as GDNF (glial cell-line derived neurotrophic factor) and other related proteins to the encoded receptor stimulates receptor dimerization and activation of downstream signaling pathways that play a role in cell differentiation, growth, migration and survival. The encoded receptor is important in development of the nervous system, and the development of organs and tissues derived from the neural crest. This proto-oncogene can undergo oncogenic activation through both cytogenetic rearrangement and activating point mutations. Mutations in this gene are associated with Hirschsprung disease and central hypoventilation syndrome and have been identified in patients with renal agenesis. [provided by RefSeq, Sep 2017]

RET links:

RET (HGNC:):

RET links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 10-43116778-C-T is Benign according to our data. Variant chr10-43116778-C-T is described in ClinVar as [Benign]. Clinvar id is 261396.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RET	NM_020975.6 linkuse as main transcript	c.2284+47C>T		intron_variant		ENST00000355710.8	NP_066124.1	P07949-1A0A024R7T2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RET	ENST00000355710.8 linkuse as main transcript	c.2284+47C>T		intron_variant		5	NM_020975.6	ENSP00000347942.3		P07949-1

Frequencies

GnomAD3 genomes

AF:

0.192

AC:

28747

AN:

149430

Hom.:

3405

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0576

Gnomad AMI

AF:

0.316

Gnomad AMR

AF:

0.200

Gnomad ASJ

AF:

0.248

Gnomad EAS

AF:

0.0556

Gnomad SAS

AF:

0.129

Gnomad FIN

AF:

0.197

Gnomad MID

AF:

0.154

Gnomad NFE

AF:

0.282

Gnomad OTH

AF:

0.188

GnomAD3 exomes

AF:

0.207

AC:

46581

AN:

224580

Hom.:

5772

AF XY:

0.211

AC XY:

25863

AN XY:

122806

show subpopulations

Gnomad AFR exome

AF:

0.0519

Gnomad AMR exome

AF:

0.182

Gnomad ASJ exome

AF:

0.248

Gnomad EAS exome

AF:

0.0586

Gnomad SAS exome

AF:

0.133

Gnomad FIN exome

AF:

0.205

Gnomad NFE exome

AF:

0.278

Gnomad OTH exome

AF:

0.218

GnomAD4 exome

AF:

0.232

AC:

295438

AN:

1271262

Hom.:

37428

Cov.:

AF XY:

0.232

AC XY:

146784

AN XY:

633670

show subpopulations

Gnomad4 AFR exome

AF:

0.0399

Gnomad4 AMR exome

AF:

0.186

Gnomad4 ASJ exome

AF:

0.236

Gnomad4 EAS exome

AF:

0.0585

Gnomad4 SAS exome

AF:

0.135

Gnomad4 FIN exome

AF:

0.198

Gnomad4 NFE exome

AF:

0.258

Gnomad4 OTH exome

AF:

0.215

GnomAD4 genome

AF:

0.192

AC:

28737

AN:

149532

Hom.:

3404

Cov.:

AF XY:

0.187

AC XY:

13598

AN XY:

72910

show subpopulations

Gnomad4 AFR

AF:

0.0574

Gnomad4 AMR

AF:

0.200

Gnomad4 ASJ

AF:

0.248

Gnomad4 EAS

AF:

0.0557

Gnomad4 SAS

AF:

0.130

Gnomad4 FIN

AF:

0.197

Gnomad4 NFE

AF:

0.282

Gnomad4 OTH

AF:

0.186

Alfa

AF:

0.148

Hom.:

447

Bravo

AF:

0.188

Asia WGS

AF:

0.105

AC:

368

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Multiple endocrine neoplasia type 2B

Benign:1

Benign, criteria provided, single submitter

clinical testing

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Jul 07, 2023

- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.38

DANN

Benign

0.87

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