rs231200

Positions:

• chr4-1991279-A-C
• chr4-1991279-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005663.5(NELFA):​c.382+265T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 152,006 control chromosomes in the GnomAD database, including 5,313 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 0.26 (5313 hom., cov: 32)
• Consequence: NELFA NM_005663.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.319

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.297 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NELFA	NM_005663.5	c.382+265T>G		intron_variant		ENST00000382882.9
NELFA	XM_017008589.3	c.466+265T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NELFA	ENST00000382882.9	c.382+265T>G		intron_variant		1	NM_005663.5	P1

Frequencies

GnomAD3 genomes AF: 0.262 AC: 39808 AN: 151890 Hom.: 5308 Cov.: 32

Gnomad AFR AF: 0.251

Gnomad AMI AF: 0.393

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.313

Gnomad EAS AF: 0.310

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.193

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.280

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.262 AC: 39855 AN: 152006 Hom.: 5313 Cov.: 32 AF XY: 0.259 AC XY: 19271 AN XY: 74320

Gnomad4 AFR AF: 0.252

Gnomad4 AMR AF: 0.269

Gnomad4 ASJ AF: 0.313

Gnomad4 EAS AF: 0.310

Gnomad4 SAS AF: 0.225

Gnomad4 FIN AF: 0.193

Gnomad4 NFE AF: 0.272

Gnomad4 OTH AF: 0.281

Alfa AF: 0.0922 Hom.: 142

Bravo AF: 0.271

Asia WGS AF: 0.324 AC: 1124 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.7
DANN	Benign	0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

Other links and lift over

dbSNP: rs231200; hg19: chr4-1993006;