rs522162

Positions:

• chr6-31952140-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002904.6(NELFE):​c.*161A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0999 in 1,507,040 control chromosomes in the GnomAD database, including 8,468 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.12 (1240 hom., cov: 32)
  • Exomes 𝑓: 0.098 (7228 hom.)
• Consequence: NELFE NM_002904.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.114

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 6-31952140-T-C is Benign according to our data. Variant chr6-31952140-T-C is described in ClinVar as [Benign]. Clinvar id is 1227313.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NELFE	NM_002904.6	c.*161A>G		3_prime_UTR_variant	11/11	ENST00000375429.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NELFE	ENST00000375429.8	c.*161A>G		3_prime_UTR_variant	11/11	1	NM_002904.6	P1

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17861 AN: 152102 Hom.: 1242 Cov.: 32

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.0461

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.0573

Gnomad EAS AF: 0.0625

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.0578

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0910

Gnomad OTH AF: 0.131

GnomAD4 exome AF: 0.0980 AC: 132714 AN: 1354820 Hom.: 7228 Cov.: 21 AF XY: 0.0988 AC XY: 67002 AN XY: 677834

Gnomad4 AFR exome AF: 0.190

Gnomad4 AMR exome AF: 0.0743

Gnomad4 ASJ exome AF: 0.0557

Gnomad4 EAS exome AF: 0.0740

Gnomad4 SAS exome AF: 0.150

Gnomad4 FIN exome AF: 0.0651

Gnomad4 NFE exome AF: 0.0950

Gnomad4 OTH exome AF: 0.109

GnomAD4 genome AF: 0.117 AC: 17882 AN: 152220 Hom.: 1240 Cov.: 32 AF XY: 0.115 AC XY: 8583 AN XY: 74452

Gnomad4 AFR AF: 0.193

Gnomad4 AMR AF: 0.102

Gnomad4 ASJ AF: 0.0573

Gnomad4 EAS AF: 0.0625

Gnomad4 SAS AF: 0.133

Gnomad4 FIN AF: 0.0578

Gnomad4 NFE AF: 0.0910

Gnomad4 OTH AF: 0.130

Alfa AF: 0.0971 Hom.: 675

Bravo AF: 0.124

Asia WGS AF: 0.155 AC: 536 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	7.9
DANN	Benign	0.72

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: rs522162; hg19: chr6-31919917; COSMIC: COSV64887977; COSMIC: COSV64887977;