6-31954663-TGTCTCGATCCCG-TGTCTCGATCCCGGTCTCGATCCCG

Variant names:

• chr6-31954663-T-TGTCTCGATCCCG
• rs377559803
• NM_002904.6:c.622_633dupCGGGATCGAGAC

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP3

The NM_002904.6(NELFE):​c.622_633dupCGGGATCGAGAC​(p.Asp211_Arg212insArgAspArgAsp) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000483 in 1,449,894 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: NELFE NM_002904.6 conservative_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.37
• Publications: 0 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: Likely_benign. The variant received -1 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_002904.6

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NELFE	NM_002904.6	MANE Select	c.622_633dupCGGGATCGAGAC	p.Asp211_Arg212insArgAspArgAsp	conservative_inframe_insertion	Exon 7 of 11	NP_002895.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NELFE	ENST00000375429.8	TSL:1 MANE Select	c.622_633dupCGGGATCGAGAC	p.Asp211_Arg212insArgAspArgAsp	conservative_inframe_insertion	Exon 7 of 11	ENSP00000364578.3	P18615-1
	NELFE	ENST00000375425.9	TSL:2	c.643_654dupCGGGATCGAGAC	p.Asp218_Arg219insArgAspArgAsp	conservative_inframe_insertion	Exon 7 of 11	ENSP00000364574.5	P18615-3
	NELFE	ENST00000948308.1		c.640_651dupCGGGATCGAGAC	p.Asp217_Arg218insArgAspArgAsp	conservative_inframe_insertion	Exon 8 of 12	ENSP00000618367.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000811 AC: 2 AN: 246680 AF XY: 0.0000150

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000905

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 0.00000483 AC: 7 AN: 1449894 Hom.: 0 Cov.: 32 AF XY: 0.00000416 AC XY: 3 AN XY: 720956

African (AFR) AF: 0.00 AC: 0 AN: 33082

American (AMR) AF: 0.00 AC: 0 AN: 43906

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25754

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39494

South Asian (SAS) AF: 0.0000118 AC: 1 AN: 84990

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51476

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5586

European-Non Finnish (NFE) AF: 0.00000362 AC: 4 AN: 1105684

Other (OTH) AF: 0.0000167 AC: 1 AN: 59922

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.4

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs377559803; hg19: chr6-31922440;