Variant 4-1983941-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_005663.5(NELFA):c.1209C>T(p.Val403Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00528 in 1,610,990 control chromosomes in the GnomAD database, including 189 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.021 ( 87 hom., cov: 33)

Exomes 𝑓: 0.0036 ( 102 hom. )

Consequence

NELFA
NM_005663.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.494

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 4-1983941-G-A is Benign according to our data. Variant chr4-1983941-G-A is described in ClinVar as [Benign]. Clinvar id is 771140.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.494 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0656 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NELFA	NM_005663.5 linkuse as main transcript	c.1209C>T	p.Val403Val	synonymous_variant	9/11	ENST00000382882.9	NP_005654.4	Q9H3P2-1A0A0C4DFX9
NELFA	XM_017008589.3 linkuse as main transcript	c.1293C>T	p.Val431Val	synonymous_variant	10/12		XP_016864078.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NELFA	ENST00000382882.9 linkuse as main transcript	c.1209C>T	p.Val403Val	synonymous_variant	9/11	1	NM_005663.5	ENSP00000372335.4		Q9H3P2-1

Frequencies

GnomAD3 genomes

AF:

0.0210

AC:

3202

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0677

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00968

Gnomad ASJ

AF:

0.00374

Gnomad EAS

AF:

0.0162

Gnomad SAS

AF:

0.00517

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00119

Gnomad OTH

AF:

0.0191

GnomAD3 exomes

AF:

0.00778

AC:

1905

AN:

244786

Hom.:

AF XY:

0.00632

AC XY:

838

AN XY:

132628

show subpopulations

Gnomad AFR exome

AF:

0.0686

Gnomad AMR exome

AF:

0.00532

Gnomad ASJ exome

AF:

0.00265

Gnomad EAS exome

AF:

0.0153

Gnomad SAS exome

AF:

0.00496

Gnomad FIN exome

AF:

0.0000485

Gnomad NFE exome

AF:

0.00116

Gnomad OTH exome

AF:

0.00668

GnomAD4 exome

AF:

0.00363

AC:

5301

AN:

1458636

Hom.:

102

Cov.:

AF XY:

0.00346

AC XY:

2508

AN XY:

725662

show subpopulations

Gnomad4 AFR exome

AF:

0.0682

Gnomad4 AMR exome

AF:

0.00522

Gnomad4 ASJ exome

AF:

0.00239

Gnomad4 EAS exome

AF:

0.0217

Gnomad4 SAS exome

AF:

0.00586

Gnomad4 FIN exome

AF:

0.0000958

Gnomad4 NFE exome

AF:

0.000741

Gnomad4 OTH exome

AF:

0.00690

GnomAD4 genome

AF:

0.0211

AC:

3208

AN:

152354

Hom.:

Cov.:

AF XY:

0.0197

AC XY:

1469

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.0677

Gnomad4 AMR

AF:

0.00967

Gnomad4 ASJ

AF:

0.00374

Gnomad4 EAS

AF:

0.0162

Gnomad4 SAS

AF:

0.00538

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00119

Gnomad4 OTH

AF:

0.0189

Alfa

AF:

0.0109

Hom.:

Bravo

AF:

0.0236

Asia WGS

AF:

0.0140

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

3.6

DANN

Benign

0.79

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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