chr6-31954663-TGTCTCGATCCCG-T

Position:

• chr6-31954663-TGTCTCGATCCCG-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_002904.6(NELFE):​c.622_633del​(p.Asp211_Arg214del) variant causes a 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 inframe_deletion
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.61

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 -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 male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 15 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NELFE	NM_002904.6	c.622_633del	p.Asp211_Arg214del	inframe_deletion	7/11	ENST00000375429.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NELFE	ENST00000375429.8	c.622_633del	p.Asp211_Arg214del	inframe_deletion	7/11	1	NM_002904.6	P1

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

GnomAD3 exomes AF: 0.00794 AC: 1959 AN: 246680 Hom.: 28 AF XY: 0.00852 AC XY: 1138 AN XY: 133572

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 SAS exome AF: 0.0219

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

Gnomad4 AFR exome AF: 0.00115

Gnomad4 AMR exome AF: 0.00979

Gnomad4 ASJ exome AF: 0.00116

Gnomad4 EAS exome AF: 0.00717

Gnomad4 SAS exome AF: 0.0230

Gnomad4 FIN exome AF: 0.00563

Gnomad4 NFE exome AF: 0.00747

Gnomad4 OTH exome AF: 0.0157

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

Gnomad4 AFR AF: 0.00203

Gnomad4 AMR AF: 0.00944

Gnomad4 ASJ AF: 0.000295

Gnomad4 EAS AF: 0.0141

Gnomad4 SAS AF: 0.0211

Gnomad4 FIN AF: 0.00382

Gnomad4 NFE AF: 0.00696

Gnomad4 OTH AF: 0.0136

Alfa AF: 0.00117 Hom.: 0

Bravo AF: 0.00565

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

Labcorp Genetics (formerly Invitae), Labcorp

Apr 09, 2018

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs377559803; hg19: chr6-31922440;