rs3034718
Positions:
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1
The NM_005663.5(NELFA):c.635-60_635-59insAG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 1,608,472 control chromosomes in the GnomAD database, including 42,970 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.27 ( 6426 hom., cov: 22)
Exomes 𝑓: 0.22 ( 36544 hom. )
Consequence
NELFA
NM_005663.5 intron
NM_005663.5 intron
Scores
Not classified
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.292
Genes affected
NELFA (HGNC:12768): (negative elongation factor complex member A) This gene is expressed ubiquitously with higher levels in fetal than in adult tissues. It encodes a protein sharing 93% sequence identity with the mouse protein. Wolf-Hirschhorn syndrome (WHS) is a malformation syndrome associated with a hemizygous deletion of the distal short arm of chromosome 4. This gene is mapped to the 165 kb WHS critical region, and may play a role in the phenotype of the WHS or Pitt-Rogers-Danks syndrome. The encoded protein is found to be capable of reacting with HLA-A2-restricted and tumor-specific cytotoxic T lymphocytes, suggesting a target for use in specific immunotherapy for a large number of cancer patients. This protein has also been shown to be a member of the NELF (negative elongation factor) protein complex that participates in the regulation of RNA polymerase II transcription elongation. [provided by RefSeq, Jul 2008]
MIR943 (HGNC:33689): (microRNA 943) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.423 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NELFA | NM_005663.5 | c.635-60_635-59insAG | intron_variant | ENST00000382882.9 | |||
MIR943 | NR_030641.1 | n.16_17insAG | non_coding_transcript_exon_variant | 1/1 | |||
NELFA | XM_017008589.3 | c.719-60_719-59insAG | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NELFA | ENST00000382882.9 | c.635-60_635-59insAG | intron_variant | 1 | NM_005663.5 | P1 | |||
MIR943 | ENST00000401286.1 | n.16_17insAG | non_coding_transcript_exon_variant | 1/1 |
Frequencies
GnomAD3 genomes ? AF: 0.273 AC: 41533AN: 151894Hom.: 6405 Cov.: 22
GnomAD3 genomes
?
AF:
AC:
41533
AN:
151894
Hom.:
Cov.:
22
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.216 AC: 51654AN: 239416Hom.: 5984 AF XY: 0.208 AC XY: 27036AN XY: 129986
GnomAD3 exomes
AF:
AC:
51654
AN:
239416
Hom.:
AF XY:
AC XY:
27036
AN XY:
129986
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.219 AC: 318932AN: 1456460Hom.: 36544 Cov.: 32 AF XY: 0.215 AC XY: 155797AN XY: 724210
GnomAD4 exome
AF:
AC:
318932
AN:
1456460
Hom.:
Cov.:
32
AF XY:
AC XY:
155797
AN XY:
724210
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.274 AC: 41608AN: 152012Hom.: 6426 Cov.: 22 AF XY: 0.267 AC XY: 19871AN XY: 74296
GnomAD4 genome
?
AF:
AC:
41608
AN:
152012
Hom.:
Cov.:
22
AF XY:
AC XY:
19871
AN XY:
74296
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
884
AN:
3478
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at