NM_002904.6:c.622_633delCGGGATCGAGAC

Variant names:

• chr6-31954663-TGTCTCGATCCCG-T
• rs377559803
• NM_002904.6:c.622_633delCGGGATCGAGAC

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP3 BP6_Moderate BS1 BS2

The NM_002904.6(NELFE):​c.622_633delCGGGATCGAGAC​(p.Arg208_Asp211del) variant causes a conservative inframe deletion change. The variant allele was found at a frequency of 0.00828 in 1,599,248 control chromosomes in the GnomAD database, including 161 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0065 (15 hom., cov: 31)
  • Exomes 𝑓: 0.0085 (146 hom.)
• Consequence: NELFE NM_002904.6 conservative_inframe_deletion
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.61
• 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: Benign. The variant received -11 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_002904.6
• BP6: Variant 6-31954663-TGTCTCGATCCCG-T is Benign according to our data. Variant chr6-31954663-TGTCTCGATCCCG-T is described in ClinVar as Benign. ClinVar VariationId is 770727.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00653 (976/149454) while in subpopulation SAS AF = 0.0211 (98/4642). AF 95% confidence interval is 0.0177. There are 15 homozygotes in GnomAd4. There are 454 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 15 gene

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_633delCGGGATCGAGAC	p.Arg208_Asp211del	conservative_inframe_deletion	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_633delCGGGATCGAGAC	p.Arg208_Asp211del	conservative_inframe_deletion	Exon 7 of 11	ENSP00000364578.3	P18615-1
	NELFE	ENST00000375425.9	TSL:2	c.643_654delCGGGATCGAGAC	p.Arg215_Asp218del	conservative_inframe_deletion	Exon 7 of 11	ENSP00000364574.5	P18615-3
	NELFE	ENST00000948308.1		c.640_651delCGGGATCGAGAC	p.Arg214_Asp217del	conservative_inframe_deletion	Exon 8 of 12	ENSP00000618367.1

Frequencies

GnomAD3 genomes AF: 0.00645 AC: 963 AN: 149370 Hom.: 13 Cov.: 31

Gnomad AFR AF: 0.00203

Gnomad AMI AF: 0.0509

Gnomad AMR AF: 0.00932

Gnomad ASJ AF: 0.000295

Gnomad EAS AF: 0.0141

Gnomad SAS AF: 0.0207

Gnomad FIN AF: 0.00382

Gnomad MID AF: 0.0132

Gnomad NFE AF: 0.00696

Gnomad OTH AF: 0.00881

GnomAD2 exomes AF: 0.00794 AC: 1959 AN: 246680 AF XY: 0.00852

Gnomad AFR exome AF: 0.00181

Gnomad AMR exome AF: 0.00780

Gnomad ASJ exome AF: 0.00110

Gnomad EAS exome AF: 0.00898

Gnomad FIN exome AF: 0.00424

Gnomad NFE exome AF: 0.00611

Gnomad OTH exome AF: 0.0102

GnomAD4 exome AF: 0.00846 AC: 12264 AN: 1449794 Hom.: 146 AF XY: 0.00888 AC XY: 6401 AN XY: 720894

African (AFR) AF: 0.00115 AC: 38 AN: 33082

American (AMR) AF: 0.00979 AC: 430 AN: 43900

Ashkenazi Jewish (ASJ) AF: 0.00116 AC: 30 AN: 25754

East Asian (EAS) AF: 0.00717 AC: 283 AN: 39492

South Asian (SAS) AF: 0.0230 AC: 1956 AN: 84960

European-Finnish (FIN) AF: 0.00563 AC: 290 AN: 51474

Middle Eastern (MID) AF: 0.00627 AC: 35 AN: 5586

European-Non Finnish (NFE) AF: 0.00747 AC: 8264 AN: 1105632

Other (OTH) AF: 0.0157 AC: 938 AN: 59914

GnomAD4 genome AF: 0.00653 AC: 976 AN: 149454 Hom.: 15 Cov.: 31 AF XY: 0.00623 AC XY: 454 AN XY: 72860

African (AFR) AF: 0.00203 AC: 83 AN: 40980

American (AMR) AF: 0.00944 AC: 142 AN: 15036

Ashkenazi Jewish (ASJ) AF: 0.000295 AC: 1 AN: 3392

East Asian (EAS) AF: 0.0141 AC: 71 AN: 5026

South Asian (SAS) AF: 0.0211 AC: 98 AN: 4642

European-Finnish (FIN) AF: 0.00382 AC: 40 AN: 10480

Middle Eastern (MID) AF: 0.0106 AC: 3 AN: 282

European-Non Finnish (NFE) AF: 0.00696 AC: 464 AN: 66650

Other (OTH) AF: 0.0136 AC: 28 AN: 2062

Alfa AF: 0.00117 Hom.: 0

Bravo AF: 0.00565

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.6
Mutation Taster		=191/9	polymorphism (auto)

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; COSMIC: COSV64810409; COSMIC: COSV64810409;