Genetic Variant NELFE:p.Arg208_Asp211del (chr6-31954663-TGTCTCGATCCCG-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

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. 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

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.61

Variant links:

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 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 6-31954663-TGTCTCGATCCCG-T is Benign according to our data. Variant chr6-31954663-TGTCTCGATCCCG-T is described in ClinVar as [Benign]. Clinvar id 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 FAILED quality control check.

BS2

High Homozygotes in GnomAd4 at 15 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NELFE	NM_002904.6 link	c.622_633delCGGGATCGAGAC	p.Arg208_Asp211del	conservative_inframe_deletion	Exon 7 of 11	ENST00000375429.8	NP_002895.3	P18615-1A0A1U9X830

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NELFE	ENST00000375429.8 link	c.622_633delCGGGATCGAGAC	p.Arg208_Asp211del	conservative_inframe_deletion	Exon 7 of 11	1	NM_002904.6	ENSP00000364578.3		P18615-1

Frequencies

GnomAD3 genomes

AF:

0.00645

AC:

963

AN:

149370

Hom.:

Cov.:

show subpopulations

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

show subpopulations

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

show subpopulations

Gnomad4 AFR exome

AF:

0.00115

AC:

AN:

33082

Gnomad4 AMR exome

AF:

0.00979

AC:

430

AN:

43900

Gnomad4 ASJ exome

AF:

0.00116

AC:

AN:

25754

Gnomad4 EAS exome

AF:

0.00717

AC:

283

AN:

39492

Gnomad4 SAS exome

AF:

0.0230

AC:

1956

AN:

84960

Gnomad4 FIN exome

AF:

0.00563

AC:

290

AN:

51474

Gnomad4 NFE exome

AF:

0.00747

AC:

8264

AN:

1105632

Gnomad4 Remaining exome

AF:

0.0157

AC:

938

AN:

59914

Heterozygous variant carriers

569

1137

1706

2274

2843

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

364

728

1092

1456

1820

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00653

AC:

976

AN:

149454

Hom.:

Cov.:

AF XY:

0.00623

AC XY:

454

AN XY:

72860

show subpopulations

Gnomad4 AFR

AF:

0.00203

AC:

0.00202538

AN:

0.00202538

Gnomad4 AMR

AF:

0.00944

AC:

0.009444

AN:

0.009444

Gnomad4 ASJ

AF:

0.000295

AC:

0.000294811

AN:

0.000294811

Gnomad4 EAS

AF:

0.0141

AC:

0.0141265

AN:

0.0141265

Gnomad4 SAS

AF:

0.0211

AC:

0.0211116

AN:

0.0211116

Gnomad4 FIN

AF:

0.00382

AC:

0.00381679

AN:

0.00381679

Gnomad4 NFE

AF:

0.00696

AC:

0.00696174

AN:

0.00696174

Gnomad4 OTH

AF:

0.0136

AC:

0.013579

AN:

0.013579

Heterozygous variant carriers

133

178

222

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00117

Hom.:

Bravo

AF:

0.00565

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Apr 09, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Mutation Taster

=191/9

polymorphism (auto)

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over