rs1077020

Positions:

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005663.5(NELFA):​c.635-64A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 1,606,562 control chromosomes in the GnomAD database, including 40,340 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 0.25 ( 5340 hom., cov: 33)
Exomes 𝑓: 0.22 ( 35000 hom. )

Consequence

NELFA
NM_005663.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.54
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.91).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.362 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NELFANM_005663.5 linkuse as main transcriptc.635-64A>G intron_variant ENST00000382882.9
MIR943NR_030641.1 linkuse as main transcriptn.12A>G non_coding_transcript_exon_variant 1/1
NELFAXM_017008589.3 linkuse as main transcriptc.719-64A>G intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NELFAENST00000382882.9 linkuse as main transcriptc.635-64A>G intron_variant 1 NM_005663.5 P1Q9H3P2-1
MIR943ENST00000401286.1 linkuse as main transcriptn.12A>G non_coding_transcript_exon_variant 1/1

Frequencies

GnomAD3 genomes
AF:
0.255
AC:
38603
AN:
151672
Hom.:
5320
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.366
Gnomad AMI
AF:
0.336
Gnomad AMR
AF:
0.235
Gnomad ASJ
AF:
0.261
Gnomad EAS
AF:
0.248
Gnomad SAS
AF:
0.130
Gnomad FIN
AF:
0.163
Gnomad MID
AF:
0.172
Gnomad NFE
AF:
0.214
Gnomad OTH
AF:
0.248
GnomAD3 exomes
AF:
0.208
AC:
49362
AN:
237856
Hom.:
5340
AF XY:
0.201
AC XY:
25984
AN XY:
129168
show subpopulations
Gnomad AFR exome
AF:
0.352
Gnomad AMR exome
AF:
0.216
Gnomad ASJ exome
AF:
0.251
Gnomad EAS exome
AF:
0.238
Gnomad SAS exome
AF:
0.127
Gnomad FIN exome
AF:
0.158
Gnomad NFE exome
AF:
0.207
Gnomad OTH exome
AF:
0.212
GnomAD4 exome
AF:
0.216
AC:
313524
AN:
1454770
Hom.:
35000
Cov.:
32
AF XY:
0.212
AC XY:
153173
AN XY:
723204
show subpopulations
Gnomad4 AFR exome
AF:
0.367
Gnomad4 AMR exome
AF:
0.224
Gnomad4 ASJ exome
AF:
0.251
Gnomad4 EAS exome
AF:
0.261
Gnomad4 SAS exome
AF:
0.131
Gnomad4 FIN exome
AF:
0.167
Gnomad4 NFE exome
AF:
0.216
Gnomad4 OTH exome
AF:
0.228
GnomAD4 genome
AF:
0.255
AC:
38675
AN:
151792
Hom.:
5340
Cov.:
33
AF XY:
0.250
AC XY:
18519
AN XY:
74176
show subpopulations
Gnomad4 AFR
AF:
0.367
Gnomad4 AMR
AF:
0.235
Gnomad4 ASJ
AF:
0.261
Gnomad4 EAS
AF:
0.247
Gnomad4 SAS
AF:
0.129
Gnomad4 FIN
AF:
0.163
Gnomad4 NFE
AF:
0.214
Gnomad4 OTH
AF:
0.248
Alfa
AF:
0.234
Hom.:
3909
Bravo
AF:
0.269
Asia WGS
AF:
0.241
AC:
837
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.91
CADD
Benign
1.6
DANN
Benign
0.56

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.

Other links and lift over

dbSNP: rs1077020; hg19: chr4-1988193; COSMIC: COSV56388603; COSMIC: COSV56388603; API