6-31952910-C-T

Variant names:

• chr6-31952910-C-T
• rs550513
• NM_002904.6:c.1046-512G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 28 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002904.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NELFE	NM_002904.6	MANE Select	c.1046-512G>A		intron	N/A	NP_002895.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NELFE	ENST00000375429.8	TSL:1 MANE Select	c.1046-512G>A		intron	N/A	ENSP00000364578.3
	NELFE	ENST00000375425.9	TSL:2	c.1067-512G>A		intron	N/A	ENSP00000364574.5
	NELFE	ENST00000948308.1		c.1064-512G>A		intron	N/A	ENSP00000618367.1

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

African (AFR) AF: 0.193 AC: 8001 AN: 41480

American (AMR) AF: 0.101 AC: 1547 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0573 AC: 199 AN: 3470

East Asian (EAS) AF: 0.0625 AC: 324 AN: 5182

South Asian (SAS) AF: 0.134 AC: 644 AN: 4820

European-Finnish (FIN) AF: 0.0574 AC: 610 AN: 10618

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0910 AC: 6188 AN: 68008

Other (OTH) AF: 0.131 AC: 276 AN: 2112

Alfa AF: 0.0953 Hom.: 1432

Bravo AF: 0.124

Asia WGS AF: 0.155 AC: 536 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.19
DANN	Benign	0.55
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs550513; hg19: chr6-31920687;