rs114747882

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_022455.5(NSD1):c.1515T>C(p.Asn505Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00118 in 1,613,988 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0063 ( 13 hom., cov: 32)

Exomes 𝑓: 0.00065 ( 6 hom. )

Consequence

NSD1
NM_022455.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.679

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:

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=-0.62).

BP6

Variant 5-177209914-T-C is Benign according to our data. Variant chr5-177209914-T-C is described in ClinVar as [Benign]. Clinvar id is 96036.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-177209914-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.679 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00634 (964/152132) while in subpopulation AFR AF= 0.0217 (902/41504). AF 95% confidence interval is 0.0206. There are 13 homozygotes in gnomad4. There are 433 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 964 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NSD1	NM_022455.5 link	c.1515T>C	p.Asn505Asn	synonymous_variant	Exon 5 of 23	ENST00000439151.7	NP_071900.2	Q96L73-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NSD1	ENST00000439151.7 link	c.1515T>C	p.Asn505Asn	synonymous_variant	Exon 5 of 23	1	NM_022455.5	ENSP00000395929.2		Q96L73-1

Frequencies

GnomAD3 genomes

AF:

0.00633

AC:

963

AN:

152014

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0218

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00341

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00337

GnomAD3 exomes

AF:

0.00162

AC:

406

AN:

250332

Hom.:

AF XY:

0.00127

AC XY:

172

AN XY:

135454

show subpopulations

Gnomad AFR exome

AF:

0.0225

Gnomad AMR exome

AF:

0.000954

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000354

Gnomad OTH exome

AF:

0.000656

GnomAD4 exome

AF:

0.000648

AC:

947

AN:

1461856

Hom.:

Cov.:

AF XY:

0.000615

AC XY:

447

AN XY:

727220

show subpopulations

Gnomad4 AFR exome

AF:

0.0226

Gnomad4 AMR exome

AF:

0.00125

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000139

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000315

Gnomad4 OTH exome

AF:

0.00124

GnomAD4 genome

AF:

0.00634

AC:

964

AN:

152132

Hom.:

Cov.:

AF XY:

0.00582

AC XY:

433

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.0217

Gnomad4 AMR

AF:

0.00341

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00333

Alfa

AF:

0.00369

Hom.:

Bravo

AF:

0.00738

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Apr 24, 2013

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 08, 2013

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Sotos syndrome

Benign:2

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 06, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Inborn genetic diseases

Benign:1

Jan 16, 2017

Ambry Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

6.3

DANN

Benign

0.57

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