Variant rs79098301 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_022455.5(NSD1):c.5623-22G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0515 in 1,613,924 control chromosomes in the GnomAD database, including 2,509 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.049 ( 200 hom., cov: 32)

Exomes 𝑓: 0.052 ( 2309 hom. )

Consequence

NSD1
NM_022455.5 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -2.49

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:

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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=-0.94).

BP6

Variant 5-177280543-G-A is Benign according to our data. Variant chr5-177280543-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 261592.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-177280543-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0748 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.5623-22G>A		intron_variant		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.5623-22G>A		intron_variant		1	NM_022455.5	ENSP00000395929.2		Q96L73-1

Frequencies

GnomAD3 genomes

AF:

0.0487

AC:

7408

AN:

152196

Hom.:

199

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0549

Gnomad AMI

AF:

0.0406

Gnomad AMR

AF:

0.0325

Gnomad ASJ

AF:

0.0153

Gnomad EAS

AF:

0.0177

Gnomad SAS

AF:

0.0815

Gnomad FIN

AF:

0.0419

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0516

Gnomad OTH

AF:

0.0435

GnomAD3 exomes

AF:

0.0467

AC:

11660

AN:

249900

Hom.:

350

AF XY:

0.0485

AC XY:

6564

AN XY:

135240

show subpopulations

Gnomad AFR exome

AF:

0.0593

Gnomad AMR exome

AF:

0.0199

Gnomad ASJ exome

AF:

0.0186

Gnomad EAS exome

AF:

0.0190

Gnomad SAS exome

AF:

0.0859

Gnomad FIN exome

AF:

0.0435

Gnomad NFE exome

AF:

0.0500

Gnomad OTH exome

AF:

0.0469

GnomAD4 exome

AF:

0.0518

AC:

75708

AN:

1461610

Hom.:

2309

Cov.:

AF XY:

0.0528

AC XY:

38364

AN XY:

727132

show subpopulations

Gnomad4 AFR exome

AF:

0.0569

Gnomad4 AMR exome

AF:

0.0218

Gnomad4 ASJ exome

AF:

0.0194

Gnomad4 EAS exome

AF:

0.0173

Gnomad4 SAS exome

AF:

0.0836

Gnomad4 FIN exome

AF:

0.0446

Gnomad4 NFE exome

AF:

0.0527

Gnomad4 OTH exome

AF:

0.0515

GnomAD4 genome

AF:

0.0487

AC:

7417

AN:

152314

Hom.:

200

Cov.:

AF XY:

0.0478

AC XY:

3560

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.0549

Gnomad4 AMR

AF:

0.0325

Gnomad4 ASJ

AF:

0.0153

Gnomad4 EAS

AF:

0.0177

Gnomad4 SAS

AF:

0.0814

Gnomad4 FIN

AF:

0.0419

Gnomad4 NFE

AF:

0.0515

Gnomad4 OTH

AF:

0.0458

Alfa

AF:

0.0498

Hom.:

Bravo

AF:

0.0469

Asia WGS

AF:

0.0930

AC:

324

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

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

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Sotos syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.0020

DANN

Benign

0.62

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