rs11740250

Positions:

chr5-177294271-G-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_022455.5(NSD1):c.6903G>C(p.Gly2301Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 1,614,014 control chromosomes in the GnomAD database, including 39,971 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2862 hom., cov: 32)

Exomes 𝑓: 0.22 ( 37109 hom. )

Consequence

NSD1
NM_022455.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -0.256

Variant links:

Genes affected

NSD1 (HGNC:14234): (nuclear receptor binding SET domain protein 1) This gene encodes a protein containing a SET domain, 2 LXXLL motifs, 3 nuclear translocation signals (NLSs), 4 plant homeodomain (PHD) finger regions, and a proline-rich region. The encoded protein enhances androgen receptor (AR) transactivation, and this enhancement can be increased further in the presence of other androgen receptor associated coregulators. This protein may act as a nucleus-localized, basic transcriptional factor and also as a bifunctional transcriptional regulator. Mutations of this gene have been associated with Sotos syndrome and Weaver syndrome. One version of childhood acute myeloid leukemia is the result of a cryptic translocation with the breakpoints occurring within nuclear receptor-binding Su-var, enhancer of zeste, and trithorax domain protein 1 on chromosome 5 and nucleoporin, 98-kd on chromosome 11. Multiple transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Sep 2018]

NSD1 links:

NSD1 (HGNC:):

NSD1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 5-177294271-G-C is Benign according to our data. Variant chr5-177294271-G-C is described in ClinVar as [Benign]. Clinvar id is 96074.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-177294271-G-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.256 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.234 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NSD1	NM_022455.5 linkuse as main transcript	c.6903G>C	p.Gly2301Gly	synonymous_variant	23/23	ENST00000439151.7	NP_071900.2	Q96L73-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NSD1	ENST00000439151.7 linkuse as main transcript	c.6903G>C	p.Gly2301Gly	synonymous_variant	23/23	1	NM_022455.5	ENSP00000395929.2		Q96L73-1

Frequencies

GnomAD3 genomes

AF:

0.168

AC:

25488

AN:

152058

Hom.:

2864

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0403

Gnomad AMI

AF:

0.244

Gnomad AMR

AF:

0.147

Gnomad ASJ

AF:

0.317

Gnomad EAS

AF:

0.00192

Gnomad SAS

AF:

0.197

Gnomad FIN

AF:

0.255

Gnomad MID

AF:

0.269

Gnomad NFE

AF:

0.237

Gnomad OTH

AF:

0.181

GnomAD3 exomes

AF:

0.190

AC:

47522

AN:

250650

Hom.:

5530

AF XY:

0.199

AC XY:

27031

AN XY:

135654

show subpopulations

Gnomad AFR exome

AF:

0.0371

Gnomad AMR exome

AF:

0.0966

Gnomad ASJ exome

AF:

0.325

Gnomad EAS exome

AF:

0.000762

Gnomad SAS exome

AF:

0.217

Gnomad FIN exome

AF:

0.243

Gnomad NFE exome

AF:

0.240

Gnomad OTH exome

AF:

0.213

GnomAD4 exome

AF:

0.217

AC:

317655

AN:

1461838

Hom.:

37109

Cov.:

AF XY:

0.218

AC XY:

158874

AN XY:

727210

show subpopulations

Gnomad4 AFR exome

AF:

0.0334

Gnomad4 AMR exome

AF:

0.104

Gnomad4 ASJ exome

AF:

0.326

Gnomad4 EAS exome

AF:

0.000605

Gnomad4 SAS exome

AF:

0.219

Gnomad4 FIN exome

AF:

0.245

Gnomad4 NFE exome

AF:

0.232

Gnomad4 OTH exome

AF:

0.209

GnomAD4 genome

AF:

0.167

AC:

25476

AN:

152176

Hom.:

2862

Cov.:

AF XY:

0.165

AC XY:

12296

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.0402

Gnomad4 AMR

AF:

0.147

Gnomad4 ASJ

AF:

0.317

Gnomad4 EAS

AF:

0.00193

Gnomad4 SAS

AF:

0.197

Gnomad4 FIN

AF:

0.255

Gnomad4 NFE

AF:

0.237

Gnomad4 OTH

AF:

0.179

Alfa

AF:

0.224

Hom.:

1390

Bravo

AF:

0.153

Asia WGS

AF:

0.0870

AC:

304

AN:

3478

EpiCase

AF:

0.245

EpiControl

AF:

0.251

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Feb 08, 2013	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jul 03, 2014	- -

Sotos syndrome

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 05, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Nov 01, 2022	- -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 16, 2016

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

3.0

DANN

Benign

0.63

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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