chr6-31954568-CTCTCGG-C

Position:

• chr6-31954568-CTCTCGG-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_002904.6(NELFE):​c.723_728del​(p.Asp241_Arg242del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.00475 in 1,607,668 control chromosomes in the GnomAD database, including 284 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.025 (135 hom., cov: 31)
  • Exomes 𝑓: 0.0027 (149 hom.)
• Consequence: NELFE NM_002904.6 inframe_deletion
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.59

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 6-31954568-CTCTCGG-C is Benign according to our data. Variant chr6-31954568-CTCTCGG-C is described in ClinVar as [Benign]. Clinvar id is 784497.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0821 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NELFE	NM_002904.6	c.723_728del	p.Asp241_Arg242del	inframe_deletion	7/11	ENST00000375429.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NELFE	ENST00000375429.8	c.723_728del	p.Asp241_Arg242del	inframe_deletion	7/11	1	NM_002904.6	P1

Frequencies

GnomAD3 genomes AF: 0.0246 AC: 3745 AN: 152138 Hom.: 136 Cov.: 31

Gnomad AFR AF: 0.0846

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0106

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000412

Gnomad OTH AF: 0.0239

GnomAD3 exomes AF: 0.00687 AC: 1691 AN: 246010 Hom.: 71 AF XY: 0.00516 AC XY: 686 AN XY: 132916

Gnomad AFR exome AF: 0.0864

Gnomad AMR exome AF: 0.00605

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000741

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000407

Gnomad OTH exome AF: 0.00266

GnomAD4 exome AF: 0.00268 AC: 3894 AN: 1455412 Hom.: 149 AF XY: 0.00233 AC XY: 1688 AN XY: 723284

Gnomad4 AFR exome AF: 0.0860

Gnomad4 AMR exome AF: 0.00668

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000647

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000187

Gnomad4 OTH exome AF: 0.00700

GnomAD4 genome AF: 0.0246 AC: 3749 AN: 152256 Hom.: 135 Cov.: 31 AF XY: 0.0238 AC XY: 1774 AN XY: 74438

Gnomad4 AFR AF: 0.0844

Gnomad4 AMR AF: 0.0106

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000830

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000412

Gnomad4 OTH AF: 0.0236

Alfa AF: 0.00137 Hom.: 0

Bravo AF: 0.0288

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

May 23, 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: rs139983860; hg19: chr6-31922345;