Variant 5-177136078-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_022455.5(NSD1):c.927+48A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0251 in 1,451,320 control chromosomes in the GnomAD database, including 579 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.018 ( 33 hom., cov: 32)

Exomes 𝑓: 0.026 ( 546 hom. )

Consequence

NSD1
NM_022455.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.11

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=-0.53).

BP6

Variant 5-177136078-A-G is Benign according to our data. Variant chr5-177136078-A-G is described in ClinVar as [Benign]. Clinvar id is 261599.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-177136078-A-G is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0182 (2779/152284) while in subpopulation NFE AF= 0.0282 (1921/68020). AF 95% confidence interval is 0.0272. There are 33 homozygotes in gnomad4. There are 1333 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2779 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NSD1	NM_022455.5 linkuse as main transcript	c.927+48A>G		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.927+48A>G		intron_variant		1	NM_022455.5	ENSP00000395929.2		Q96L73-1

Frequencies

GnomAD3 genomes

AF:

0.0183

AC:

2782

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00446

Gnomad AMI

AF:

0.0296

Gnomad AMR

AF:

0.00832

Gnomad ASJ

AF:

0.00979

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.0269

Gnomad FIN

AF:

0.0301

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0283

Gnomad OTH

AF:

0.0129

GnomAD3 exomes

AF:

0.0213

AC:

4779

AN:

224242

Hom.:

AF XY:

0.0222

AC XY:

2726

AN XY:

122852

show subpopulations

Gnomad AFR exome

AF:

0.00514

Gnomad AMR exome

AF:

0.00790

Gnomad ASJ exome

AF:

0.0146

Gnomad EAS exome

AF:

0.0000631

Gnomad SAS exome

AF:

0.0298

Gnomad FIN exome

AF:

0.0317

Gnomad NFE exome

AF:

0.0274

Gnomad OTH exome

AF:

0.0214

GnomAD4 exome

AF:

0.0259

AC:

33592

AN:

1299036

Hom.:

546

Cov.:

AF XY:

0.0261

AC XY:

17057

AN XY:

653030

show subpopulations

Gnomad4 AFR exome

AF:

0.00361

Gnomad4 AMR exome

AF:

0.00820

Gnomad4 ASJ exome

AF:

0.0143

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0305

Gnomad4 FIN exome

AF:

0.0311

Gnomad4 NFE exome

AF:

0.0282

Gnomad4 OTH exome

AF:

0.0214

GnomAD4 genome

AF:

0.0182

AC:

2779

AN:

152284

Hom.:

Cov.:

AF XY:

0.0179

AC XY:

1333

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.00445

Gnomad4 AMR

AF:

0.00831

Gnomad4 ASJ

AF:

0.00979

Gnomad4 EAS

AF:

0.000578

Gnomad4 SAS

AF:

0.0267

Gnomad4 FIN

AF:

0.0301

Gnomad4 NFE

AF:

0.0282

Gnomad4 OTH

AF:

0.0128

Alfa

AF:

0.0245

Hom.:

Bravo

AF:

0.0151

Asia WGS

AF:

0.0150

AC:

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

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

-0.53

CADD

Benign

DANN

Benign

0.79

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