rs114747882
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_022455.5(NSD1):āc.1515T>Cā(p.Asn505=) 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 (ā ā ).
Frequency
Genomes: š 0.0063 ( 13 hom., cov: 32)
Exomes š: 0.00065 ( 6 hom. )
Consequence
NSD1
NM_022455.5 synonymous
NM_022455.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.679
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]
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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/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NSD1 | NM_022455.5 | c.1515T>C | p.Asn505= | synonymous_variant | 5/23 | ENST00000439151.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NSD1 | ENST00000439151.7 | c.1515T>C | p.Asn505= | synonymous_variant | 5/23 | 1 | NM_022455.5 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.00633 AC: 963AN: 152014Hom.: 13 Cov.: 32
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GnomAD3 exomes AF: 0.00162 AC: 406AN: 250332Hom.: 4 AF XY: 0.00127 AC XY: 172AN XY: 135454
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GnomAD4 exome AF: 0.000648 AC: 947AN: 1461856Hom.: 6 Cov.: 37 AF XY: 0.000615 AC XY: 447AN XY: 727220
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GnomAD4 genome ? AF: 0.00634 AC: 964AN: 152132Hom.: 13 Cov.: 32 AF XY: 0.00582 AC XY: 433AN XY: 74374
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ClinVar
Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Feb 08, 2013 | - - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Apr 24, 2013 | - - |
Sotos syndrome Benign:2
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 15, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Nov 01, 2022 | - - |
Inborn genetic diseases Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 16, 2017 | 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. - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at