Variant 5-177134112-T-C 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_022455.5(NSD1):c.-18+160T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.334 in 148,406 control chromosomes in the GnomAD database, including 11,507 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.33 ( 11506 hom., cov: 28)

Exomes 𝑓: 0.21 ( 1 hom. )

Consequence

NSD1
NM_022455.5 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.158

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 5-177134112-T-C is Benign according to our data. Variant chr5-177134112-T-C is described in ClinVar as [Benign]. Clinvar id is 1239366.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.649 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NSD1	NM_022455.5 link	c.-18+160T>C		intron_variant	Intron 1 of 22	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.-18+160T>C		intron_variant	Intron 1 of 22	1	NM_022455.5	ENSP00000395929.2		Q96L73-1

Frequencies

GnomAD3 genomes

AF:

0.333

AC:

49435

AN:

148264

Hom.:

11486

Cov.:

show subpopulations

Gnomad AFR

AF:

0.655

Gnomad AMI

AF:

0.0767

Gnomad AMR

AF:

0.263

Gnomad ASJ

AF:

0.196

Gnomad EAS

AF:

0.505

Gnomad SAS

AF:

0.306

Gnomad FIN

AF:

0.227

Gnomad MID

AF:

0.263

Gnomad NFE

AF:

0.174

Gnomad OTH

AF:

0.291

GnomAD4 exome

AF:

0.214

AC:

AN:

Hom.:

Cov.:

AF XY:

0.225

AC XY:

AN XY:

show subpopulations

Gnomad4 EAS exome

AF:

0.500

Gnomad4 NFE exome

AF:

0.194

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.334

AC:

49498

AN:

148364

Hom.:

11506

Cov.:

AF XY:

0.335

AC XY:

24284

AN XY:

72436

show subpopulations

Gnomad4 AFR

AF:

0.655

Gnomad4 AMR

AF:

0.263

Gnomad4 ASJ

AF:

0.196

Gnomad4 EAS

AF:

0.504

Gnomad4 SAS

AF:

0.307

Gnomad4 FIN

AF:

0.227

Gnomad4 NFE

AF:

0.174

Gnomad4 OTH

AF:

0.290

Alfa

AF:

0.276

Hom.:

988

Bravo

AF:

0.352

Asia WGS

AF:

0.397

AC:

1347

AN:

3408

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

May 01, 2020

GeneDx

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

-0.75

CADD

Benign

DANN

Benign

0.14

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