rs17201466

Positions:

• chr6-31958823-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_002904.6(NELFE):​c.-9+69G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0306 in 659,354 control chromosomes in the GnomAD database, including 655 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.031 (161 hom., cov: 33)
  • Exomes 𝑓: 0.030 (494 hom.)
• Consequence: NELFE NM_002904.6 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.258

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 6-31958823-C-T is Benign according to our data. Variant chr6-31958823-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 356299.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0308 (4686/152308) while in subpopulation NFE AF= 0.0361 (2454/68034). AF 95% confidence interval is 0.0349. There are 161 homozygotes in gnomad4. There are 2575 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 161 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NELFE	NM_002904.6	c.-9+69G>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.-9+69G>A		intron_variant		1	NM_002904.6	ENSP00000364578.3

Frequencies

GnomAD3 genomes AF: 0.0308 AC: 4686 AN: 152190 Hom.: 161 Cov.: 33

Gnomad AFR AF: 0.00627

Gnomad AMI AF: 0.0857

Gnomad AMR AF: 0.0124

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.0122

Gnomad FIN AF: 0.150

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0361

Gnomad OTH AF: 0.0177

GnomAD4 exome AF: 0.0305 AC: 15464 AN: 507046 Hom.: 494 Cov.: 0 AF XY: 0.0290 AC XY: 7917 AN XY: 273324

Gnomad4 AFR exome AF: 0.00545

Gnomad4 AMR exome AF: 0.00955

Gnomad4 ASJ exome AF: 0.00304

Gnomad4 EAS exome AF: 0.000189

Gnomad4 SAS exome AF: 0.00955

Gnomad4 FIN exome AF: 0.130

Gnomad4 NFE exome AF: 0.0328

Gnomad4 OTH exome AF: 0.0231

GnomAD4 genome AF: 0.0308 AC: 4686 AN: 152308 Hom.: 161 Cov.: 33 AF XY: 0.0346 AC XY: 2575 AN XY: 74464

Gnomad4 AFR AF: 0.00626

Gnomad4 AMR AF: 0.0124

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.000964

Gnomad4 SAS AF: 0.0124

Gnomad4 FIN AF: 0.150

Gnomad4 NFE AF: 0.0361

Gnomad4 OTH AF: 0.0175

Alfa AF: 0.0321 Hom.: 69

Bravo AF: 0.0191

Asia WGS AF: 0.00375 AC: 13 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Trichohepatoenteric syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	7.5
DANN	Benign	0.86
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs17201466; hg19: chr6-31926600;