rs403569

chr6-31957103-G-A

Variant summary

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

The NM_002904.6(NELFE):c.76-93C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0974 in 1,130,108 control chromosomes in the GnomAD database, including 6,292 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 (1282 hom., cov: 33)
  • Exomes 𝑓: 0.094 (5010 hom.)
• Consequence: NELFE NM_002904.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.13

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.196 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NELFE	NM_002904.6	c.76-93C>T		intron_variant		ENST00000375429.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NELFE	ENST00000375429.8	c.76-93C>T		intron_variant		1	NM_002904.6	P1

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18104 AN: 152058 Hom.: 1282 Cov.: 33

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.0462

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.0573

Gnomad EAS AF: 0.0622

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.0577

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0908

Gnomad OTH AF: 0.132

GnomAD4 exome AF: 0.0941 AC: 91988 AN: 977932 Hom.: 5010 AF XY: 0.0953 AC XY: 47081 AN XY: 494262

Gnomad4 AFR exome AF: 0.190

Gnomad4 AMR exome AF: 0.0736

Gnomad4 ASJ exome AF: 0.0549

Gnomad4 EAS exome AF: 0.0731

Gnomad4 SAS exome AF: 0.146

Gnomad4 FIN exome AF: 0.0654

Gnomad4 NFE exome AF: 0.0904

Gnomad4 OTH exome AF: 0.104

GnomAD4 genome AF: 0.119 AC: 18128 AN: 152176 Hom.: 1282 Cov.: 33 AF XY: 0.117 AC XY: 8700 AN XY: 74406

Gnomad4 AFR AF: 0.199

Gnomad4 AMR AF: 0.102

Gnomad4 ASJ AF: 0.0573

Gnomad4 EAS AF: 0.0622

Gnomad4 SAS AF: 0.134

Gnomad4 FIN AF: 0.0577

Gnomad4 NFE AF: 0.0908

Gnomad4 OTH AF: 0.131

Alfa AF: 0.0938 Hom.: 478

Bravo AF: 0.126

Asia WGS AF: 0.155 AC: 537 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	2.8
Dann	Benign	0.43

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: rs403569; hg19: chr6-31924880;