Variant 10-43100333-G-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.74-126G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.334 in 1,104,434 control chromosomes in the GnomAD database, including 65,741 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.38 ( 12401 hom., cov: 33)

Exomes 𝑓: 0.33 ( 53340 hom. )

Consequence

RET
NM_020975.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.0150

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:

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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=-0.87).

BP6

Variant 10-43100333-G-T is Benign according to our data. Variant chr10-43100333-G-T is described in ClinVar as [Benign]. Clinvar id is 677050.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.584 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.74-126G>T		intron_variant		ENST00000355710.8	NP_066124.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RET	ENST00000355710.8 linkuse as main transcript	c.74-126G>T		intron_variant		5	NM_020975.6	ENSP00000347942	P4	P07949-1

Frequencies

GnomAD3 genomes

AF:

0.381

AC:

57777

AN:

151560

Hom.:

12369

Cov.:

show subpopulations

Gnomad AFR

AF:

0.589

Gnomad AMI

AF:

0.250

Gnomad AMR

AF:

0.321

Gnomad ASJ

AF:

0.326

Gnomad EAS

AF:

0.111

Gnomad SAS

AF:

0.196

Gnomad FIN

AF:

0.234

Gnomad MID

AF:

0.255

Gnomad NFE

AF:

0.330

Gnomad OTH

AF:

0.370

GnomAD4 exome

AF:

0.326

AC:

310614

AN:

952784

Hom.:

53340

AF XY:

0.321

AC XY:

157441

AN XY:

490342

show subpopulations

Gnomad4 AFR exome

AF:

0.601

Gnomad4 AMR exome

AF:

0.263

Gnomad4 ASJ exome

AF:

0.329

Gnomad4 EAS exome

AF:

0.132

Gnomad4 SAS exome

AF:

0.218

Gnomad4 FIN exome

AF:

0.254

Gnomad4 NFE exome

AF:

0.345

Gnomad4 OTH exome

AF:

0.331

GnomAD4 genome

AF:

0.381

AC:

57854

AN:

151650

Hom.:

12401

Cov.:

AF XY:

0.371

AC XY:

27505

AN XY:

74102

show subpopulations

Gnomad4 AFR

AF:

0.590

Gnomad4 AMR

AF:

0.321

Gnomad4 ASJ

AF:

0.326

Gnomad4 EAS

AF:

0.112

Gnomad4 SAS

AF:

0.198

Gnomad4 FIN

AF:

0.234

Gnomad4 NFE

AF:

0.330

Gnomad4 OTH

AF:

0.367

Alfa

AF:

0.279

Hom.:

1591

Bravo

AF:

0.398

Asia WGS

AF:

0.187

AC:

651

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 16, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Multiple endocrine neoplasia, type 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 18, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

1.3

DANN

Benign

0.46

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