5-177264278-T-G

Position:

• chr5-177264278-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022455.5(NSD1):​c.5147-3284T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.71 in 151,880 control chromosomes in the GnomAD database, including 39,796 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.71 (39796 hom., cov: 30)
• Consequence: NSD1 NM_022455.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.628

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.818 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NSD1	NM_022455.5	c.5147-3284T>G		intron_variant		ENST00000439151.7	NP_071900.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NSD1	ENST00000439151.7	c.5147-3284T>G		intron_variant		1	NM_022455.5	ENSP00000395929.2

Frequencies

GnomAD3 genomes AF: 0.710 AC: 107807 AN: 151762 Hom.: 39795 Cov.: 30

Gnomad AFR AF: 0.506

Gnomad AMI AF: 0.902

Gnomad AMR AF: 0.758

Gnomad ASJ AF: 0.849

Gnomad EAS AF: 0.471

Gnomad SAS AF: 0.670

Gnomad FIN AF: 0.769

Gnomad MID AF: 0.847

Gnomad NFE AF: 0.824

Gnomad OTH AF: 0.753

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.710 AC: 107850 AN: 151880 Hom.: 39796 Cov.: 30 AF XY: 0.707 AC XY: 52452 AN XY: 74238

Gnomad4 AFR AF: 0.506

Gnomad4 AMR AF: 0.758

Gnomad4 ASJ AF: 0.849

Gnomad4 EAS AF: 0.472

Gnomad4 SAS AF: 0.670

Gnomad4 FIN AF: 0.769

Gnomad4 NFE AF: 0.824

Gnomad4 OTH AF: 0.751

Alfa AF: 0.808 Hom.: 48156

Bravo AF: 0.703

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.5
DANN	Benign	0.33

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

Other links and lift over

dbSNP: rs10037055; hg19: chr5-176691279; COSMIC: COSV61773319; COSMIC: COSV61773319;