rs550513

Positions:

• chr6-31952910-C-T

Variant summary

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

The NM_002904.6(NELFE):​c.1046-512G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 152,172 control chromosomes in the GnomAD database, including 1,238 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 0.12 (1238 hom., cov: 32)
• Consequence: NELFE NM_002904.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.60

Genes affected

NELFE (HGNC:13974): (negative elongation factor complex member E) The protein encoded by this gene is part of a complex termed negative elongation factor (NELF) which represses RNA polymerase II transcript elongation. This protein bears similarity to nuclear RNA-binding proteins; however, it has not been demonstrated that this protein binds RNA. The protein contains a tract of alternating basic and acidic residues, largely arginine (R) and aspartic acid (D). The gene localizes to the major histocompatibility complex (MHC) class III region on chromosome 6. [provided by RefSeq, Jul 2008]

NELFE (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NELFE	NM_002904.6	c.1046-512G>A		intron_variant		ENST00000375429.8	NP_002895.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NELFE	ENST00000375429.8	c.1046-512G>A		intron_variant		1	NM_002904.6	ENSP00000364578.3

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17838 AN: 152054 Hom.: 1240 Cov.: 32

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.0462

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.0573

Gnomad EAS AF: 0.0626

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.0574

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0910

Gnomad OTH AF: 0.132

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

GnomAD4 genome AF: 0.117 AC: 17859 AN: 152172 Hom.: 1238 Cov.: 32 AF XY: 0.115 AC XY: 8563 AN XY: 74400

Gnomad4 AFR AF: 0.193

Gnomad4 AMR AF: 0.101

Gnomad4 ASJ AF: 0.0573

Gnomad4 EAS AF: 0.0625

Gnomad4 SAS AF: 0.134

Gnomad4 FIN AF: 0.0574

Gnomad4 NFE AF: 0.0910

Gnomad4 OTH AF: 0.131

Alfa AF: 0.0892 Hom.: 883

Bravo AF: 0.124

Asia WGS AF: 0.155 AC: 536 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.19
DANN	Benign	0.55

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

Other links and lift over

dbSNP: rs550513; hg19: chr6-31920687;