Genetic Variant NELFCD:c.-11C>T (chr20-58981299-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_198976.4(NELFCD):c.-11C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000371 in 1,077,032 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000039 ( 0 hom. )

Consequence

NELFCD
NM_198976.4 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.646

Publications

0 publications found

Variant links:

Genes affected

NELFCD (HGNC:15934): (negative elongation factor complex member C/D) The NELF complex of proteins interacts with the DSIF protein complex to repress transcriptional elongation by RNA polymerase II. The protein encoded by this gene is an essential part of the NELF complex. Alternative translation initiation site usage results in the formation of two isoforms with different N-termini. [provided by RefSeq, Jul 2008]

NELFCD links:

ENSG00000285091 (HGNC:):

ENSG00000285091 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14639476).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198976.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NELFCD	NM_198976.4	MANE Select	c.-11C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 15	NP_945327.3	Q8IXH7-4
	NELFCD	NM_198976.4	MANE Select	c.-11C>T		5_prime_UTR	Exon 1 of 15	NP_945327.3	Q8IXH7-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NELFCD	ENST00000652272.2	MANE Select	c.-11C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 15	ENSP00000499018.1	Q8IXH7-4
NELFCD	ENST00000602795.6	TSL:1	c.44C>T	p.Pro15Leu	missense	Exon 1 of 15	ENSP00000473290.1	H0UI80
NELFCD	ENST00000652272.2	MANE Select	c.-11C>T		5_prime_UTR	Exon 1 of 15	ENSP00000499018.1	Q8IXH7-4

Frequencies

GnomAD3 genomes

AF:

0.0000271

AC:

AN:

147708

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000976

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000387

AC:

AN:

929324

Hom.:

Cov.:

AF XY:

0.0000274

AC XY:

AN XY:

438238

show subpopulations

African (AFR)

AF:

0.0000551

AC:

AN:

18138

American (AMR)

AF:

0.00

AC:

AN:

7448

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

7312

East Asian (EAS)

AF:

0.00

AC:

AN:

10936

South Asian (SAS)

AF:

0.00

AC:

AN:

20886

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8518

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3282

European-Non Finnish (NFE)

AF:

0.0000402

AC:

AN:

820636

Other (OTH)

AF:

0.0000622

AC:

AN:

32168

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000271

AC:

AN:

147708

Hom.:

Cov.:

AF XY:

0.0000278

AC XY:

AN XY:

71902

show subpopulations

African (AFR)

AF:

0.0000976

AC:

AN:

40984

American (AMR)

AF:

0.00

AC:

AN:

14874

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3394

East Asian (EAS)

AF:

0.00

AC:

AN:

5122

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9024

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

66226

Other (OTH)

AF:

0.00

AC:

AN:

2034

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

Bravo

AF:

0.0000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Uncertain

0.99

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.76

M_CAP

Uncertain

0.25

MetaRNN

Benign

0.15

MetaSVM

Benign

-1.1

PhyloP100

0.65

PrimateAI

Pathogenic

0.89

Sift4G

Benign

0.19

Vest4

0.27

MVP

0.30

MPC

0.66

ClinPred

0.24

GERP RS

2.0

PromoterAI

-0.0015

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.43

Mutation Taster

=96/4

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over