rs756321444
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The ENST00000439151.7(NSD1):c.5712C>T(p.Pro1904=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000855 in 1,614,078 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000089 ( 3 hom. )
Consequence
NSD1
ENST00000439151.7 synonymous
ENST00000439151.7 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.49
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=-0.5).
BP6
Variant 5-177280654-C-T is Benign according to our data. Variant chr5-177280654-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 261593.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-1.49 with no splicing effect.
BS1
Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.0000889 (130/1461892) while in subpopulation AMR AF= 0.00257 (115/44724). AF 95% confidence interval is 0.00219. There are 3 homozygotes in gnomad4_exome. There are 54 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAd4 at 8 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NSD1 | NM_022455.5 | c.5712C>T | p.Pro1904= | synonymous_variant | 18/23 | ENST00000439151.7 | NP_071900.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NSD1 | ENST00000439151.7 | c.5712C>T | p.Pro1904= | synonymous_variant | 18/23 | 1 | NM_022455.5 | ENSP00000395929 | P2 |
Frequencies
GnomAD3 genomes AF: 0.0000526 AC: 8AN: 152186Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000485 AC: 122AN: 251432Hom.: 3 AF XY: 0.000361 AC XY: 49AN XY: 135894
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GnomAD4 exome AF: 0.0000889 AC: 130AN: 1461892Hom.: 3 Cov.: 32 AF XY: 0.0000743 AC XY: 54AN XY: 727246
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GnomAD4 genome AF: 0.0000526 AC: 8AN: 152186Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74354
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Sotos syndrome Benign:2
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 15, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Nov 01, 2022 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 22, 2019 | - - |
Computational scores
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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