Variant 4-1983663-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_005663.5(NELFA):c.1335C>T(p.Phe445Phe) variant causes a synonymous change. The variant allele was found at a frequency of 0.00569 in 1,614,046 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0039 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0059 ( 34 hom. )

Consequence

NELFA
NM_005663.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 4.95

Variant links:

Genes affected

NELFA (HGNC:12768): (negative elongation factor complex member A) This gene is expressed ubiquitously with higher levels in fetal than in adult tissues. It encodes a protein sharing 93% sequence identity with the mouse protein. Wolf-Hirschhorn syndrome (WHS) is a malformation syndrome associated with a hemizygous deletion of the distal short arm of chromosome 4. This gene is mapped to the 165 kb WHS critical region, and may play a role in the phenotype of the WHS or Pitt-Rogers-Danks syndrome. The encoded protein is found to be capable of reacting with HLA-A2-restricted and tumor-specific cytotoxic T lymphocytes, suggesting a target for use in specific immunotherapy for a large number of cancer patients. This protein has also been shown to be a member of the NELF (negative elongation factor) protein complex that participates in the regulation of RNA polymerase II transcription elongation. [provided by RefSeq, Jul 2008]

NELFA links:

NELFA (HGNC:):

NELFA links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 4-1983663-G-A is Benign according to our data. Variant chr4-1983663-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 710318.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NELFA	NM_005663.5 linkuse as main transcript	c.1335C>T	p.Phe445Phe	synonymous_variant	10/11	ENST00000382882.9	NP_005654.4	Q9H3P2-1A0A0C4DFX9
NELFA	XM_017008589.3 linkuse as main transcript	c.1419C>T	p.Phe473Phe	synonymous_variant	11/12		XP_016864078.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NELFA	ENST00000382882.9 linkuse as main transcript	c.1335C>T	p.Phe445Phe	synonymous_variant	10/11	1	NM_005663.5	ENSP00000372335.4		Q9H3P2-1

Frequencies

GnomAD3 genomes

AF:

0.00392

AC:

597

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00307

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00310

Gnomad FIN

AF:

0.00160

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00654

Gnomad OTH

AF:

0.00621

GnomAD3 exomes

AF:

0.00486

AC:

1221

AN:

251254

Hom.:

AF XY:

0.00530

AC XY:

720

AN XY:

135858

show subpopulations

Gnomad AFR exome

AF:

0.00129

Gnomad AMR exome

AF:

0.00226

Gnomad ASJ exome

AF:

0.00248

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00621

Gnomad FIN exome

AF:

0.00250

Gnomad NFE exome

AF:

0.00719

Gnomad OTH exome

AF:

0.00571

GnomAD4 exome

AF:

0.00587

AC:

8579

AN:

1461718

Hom.:

Cov.:

AF XY:

0.00585

AC XY:

4252

AN XY:

727176

show subpopulations

Gnomad4 AFR exome

AF:

0.00105

Gnomad4 AMR exome

AF:

0.00266

Gnomad4 ASJ exome

AF:

0.00207

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00514

Gnomad4 FIN exome

AF:

0.00212

Gnomad4 NFE exome

AF:

0.00672

Gnomad4 OTH exome

AF:

0.00498

GnomAD4 genome

AF:

0.00392

AC:

597

AN:

152328

Hom.:

Cov.:

AF XY:

0.00357

AC XY:

266

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.00120

Gnomad4 AMR

AF:

0.00307

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00311

Gnomad4 FIN

AF:

0.00160

Gnomad4 NFE

AF:

0.00654

Gnomad4 OTH

AF:

0.00614

Alfa

AF:

0.00481

Hom.:

Bravo

AF:

0.00409

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.00709

EpiControl

AF:

0.00729

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Oct 01, 2023	NELFA: BP4, BS2 -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.87

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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