Variant 1-3069321-C-G 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_022114.4(PRDM16):c.37+25C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.392 in 1,264,322 control chromosomes in the GnomAD database, including 101,620 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.35 ( 10340 hom., cov: 27)

Exomes 𝑓: 0.40 ( 91280 hom. )

Consequence

PRDM16
NM_022114.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.240

Variant links:

Genes affected

PRDM16 (HGNC:14000): (PR/SET domain 16) The reciprocal translocation t(1;3)(p36;q21) occurs in a subset of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). This gene is located near the 1p36.3 breakpoint and has been shown to be specifically expressed in the t(1:3)(p36,q21)-positive MDS/AML. The protein encoded by this gene is a zinc finger transcription factor and contains an N-terminal PR domain. The translocation results in the overexpression of a truncated version of this protein that lacks the PR domain, which may play an important role in the pathogenesis of MDS and AML. Alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]

PRDM16 links:

LOC124903827 (HGNC:):

LOC124903827 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP6

Variant 1-3069321-C-G is Benign according to our data. Variant chr1-3069321-C-G is described in ClinVar as [Benign]. Clinvar id is 674706.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.541 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRDM16	NM_022114.4 linkuse as main transcript	c.37+25C>G		intron_variant		ENST00000270722.10
LOC124903827	XM_047436614.1 linkuse as main transcript	c.1651-350G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRDM16	ENST00000270722.10 linkuse as main transcript	c.37+25C>G		intron_variant		1	NM_022114.4	P1	Q9HAZ2-1

Frequencies

GnomAD3 genomes

AF:

0.355

AC:

50703

AN:

142982

Hom.:

10344

Cov.:

show subpopulations

Gnomad AFR

AF:

0.160

Gnomad AMI

AF:

0.305

Gnomad AMR

AF:

0.499

Gnomad ASJ

AF:

0.419

Gnomad EAS

AF:

0.560

Gnomad SAS

AF:

0.409

Gnomad FIN

AF:

0.551

Gnomad MID

AF:

0.287

Gnomad NFE

AF:

0.397

Gnomad OTH

AF:

0.354

GnomAD3 exomes

AF:

0.459

AC:

62080

AN:

135242

Hom.:

14484

AF XY:

0.451

AC XY:

34427

AN XY:

76276

show subpopulations

Gnomad AFR exome

AF:

0.172

Gnomad AMR exome

AF:

0.611

Gnomad ASJ exome

AF:

0.434

Gnomad EAS exome

AF:

0.585

Gnomad SAS exome

AF:

0.405

Gnomad FIN exome

AF:

0.538

Gnomad NFE exome

AF:

0.420

Gnomad OTH exome

AF:

0.409

GnomAD4 exome

AF:

0.397

AC:

445017

AN:

1121338

Hom.:

91280

Cov.:

AF XY:

0.397

AC XY:

218309

AN XY:

549500

show subpopulations

Gnomad4 AFR exome

AF:

0.139

Gnomad4 AMR exome

AF:

0.587

Gnomad4 ASJ exome

AF:

0.416

Gnomad4 EAS exome

AF:

0.579

Gnomad4 SAS exome

AF:

0.394

Gnomad4 FIN exome

AF:

0.521

Gnomad4 NFE exome

AF:

0.391

Gnomad4 OTH exome

AF:

0.390

GnomAD4 genome

AF:

0.354

AC:

50681

AN:

142984

Hom.:

10340

Cov.:

AF XY:

0.365

AC XY:

25374

AN XY:

69436

show subpopulations

Gnomad4 AFR

AF:

0.160

Gnomad4 AMR

AF:

0.499

Gnomad4 ASJ

AF:

0.419

Gnomad4 EAS

AF:

0.559

Gnomad4 SAS

AF:

0.410

Gnomad4 FIN

AF:

0.551

Gnomad4 NFE

AF:

0.397

Gnomad4 OTH

AF:

0.354

Alfa

AF:

0.247

Hom.:

731

Bravo

AF:

0.348

Asia WGS

AF:

0.375

AC:

1142

AN:

3050

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

Jun 15, 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

Cadd

Benign

Dann

Benign

0.66

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