Variant 4-1986461-C-CCT details in Genebe, Genetics Data Aggregator

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

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.292

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]

NELFA links:

NELFA (HGNC:):

NELFA links:

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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	Effect	#exon/exons	MANE	Protein	UniProt
NELFA	NM_005663.5 linkuse as main transcript	c.635-60_635-59insAG	intron_variant		ENST00000382882.9	NP_005654.4	Q9H3P2-1A0A0C4DFX9
NELFA	XM_017008589.3 linkuse as main transcript	c.719-60_719-59insAG	intron_variant			XP_016864078.2
MIR943	NR_030641.1 linkuse as main transcript	n.16_17insAG	non_coding_transcript_exon_variant	1/1
MIR943	unassigned_transcript_724 use as main transcript	n.-39_-38insAG	upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NELFA	ENST00000382882.9 linkuse as main transcript	c.635-60_635-59insAG		intron_variant		1	NM_005663.5	ENSP00000372335.4		Q9H3P2-1

Frequencies

GnomAD3 genomes

AF:

0.273

AC:

41533

AN:

151894

Hom.:

6405

Cov.:

show subpopulations

Gnomad AFR

AF:

0.427

Gnomad AMI

AF:

0.337

Gnomad AMR

AF:

0.244

Gnomad ASJ

AF:

0.260

Gnomad EAS

AF:

0.264

Gnomad SAS

AF:

0.135

Gnomad FIN

AF:

0.162

Gnomad MID

AF:

0.185

Gnomad NFE

AF:

0.215

Gnomad OTH

AF:

0.264

GnomAD3 exomes

AF:

0.216

AC:

51654

AN:

239416

Hom.:

5984

AF XY:

0.208

AC XY:

27036

AN XY:

129986

show subpopulations

Gnomad AFR exome

AF:

0.417

Gnomad AMR exome

AF:

0.221

Gnomad ASJ exome

AF:

0.252

Gnomad EAS exome

AF:

0.254

Gnomad SAS exome

AF:

0.133

Gnomad FIN exome

AF:

0.159

Gnomad NFE exome

AF:

0.210

Gnomad OTH exome

AF:

0.220

GnomAD4 exome

AF:

0.219

AC:

318932

AN:

1456460

Hom.:

36544

Cov.:

AF XY:

0.215

AC XY:

155797

AN XY:

724210

show subpopulations

Gnomad4 AFR exome

AF:

0.430

Gnomad4 AMR exome

AF:

0.228

Gnomad4 ASJ exome

AF:

0.252

Gnomad4 EAS exome

AF:

0.282

Gnomad4 SAS exome

AF:

0.138

Gnomad4 FIN exome

AF:

0.167

Gnomad4 NFE exome

AF:

0.217

Gnomad4 OTH exome

AF:

0.234

GnomAD4 genome

AF:

0.274

AC:

41608

AN:

152012

Hom.:

6426

Cov.:

AF XY:

0.267

AC XY:

19871

AN XY:

74296

show subpopulations

Gnomad4 AFR

AF:

0.428

Gnomad4 AMR

AF:

0.244

Gnomad4 ASJ

AF:

0.260

Gnomad4 EAS

AF:

0.263

Gnomad4 SAS

AF:

0.134

Gnomad4 FIN

AF:

0.162

Gnomad4 NFE

AF:

0.215

Gnomad4 OTH

AF:

0.264

Alfa

AF:

0.243

Hom.:

802

Bravo

AF:

0.290

Asia WGS

AF:

0.255

AC:

884

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over