Variant chr20-58993122-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_198976.4(NELFCD):c.1344+10C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00502 in 1,594,328 control chromosomes in the GnomAD database, including 334 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.027 ( 183 hom., cov: 32)

Exomes 𝑓: 0.0027 ( 151 hom. )

Consequence

NELFCD
NM_198976.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.670

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:

NELFCD (HGNC:):

NELFCD links:

CTSZ (HGNC:2547): (cathepsin Z) The protein encoded by this gene is a lysosomal cysteine proteinase and member of the peptidase C1 family. It exhibits both carboxy-monopeptidase and carboxy-dipeptidase activities. The encoded protein has also been known as cathepsin X and cathepsin P. This gene is expressed ubiquitously in cancer cell lines and primary tumors and, like other members of this family, may be involved in tumorigenesis. [provided by RefSeq, Oct 2008]

CTSZ links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 20-58993122-C-T is Benign according to our data. Variant chr20-58993122-C-T is described in ClinVar as [Benign]. Clinvar id is 784412.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0921 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NELFCD	NM_198976.4 linkuse as main transcript	c.1344+10C>T		intron_variant		ENST00000652272.2	NP_945327.3	Q8IXH7-4H0UI80
NELFCD	XM_047440188.1 linkuse as main transcript	c.1398+10C>T		intron_variant			XP_047296144.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NELFCD	ENST00000652272.2 linkuse as main transcript	c.1344+10C>T		intron_variant			NM_198976.4	ENSP00000499018.1		Q8IXH7-4

Frequencies

GnomAD3 genomes

AF:

0.0269

AC:

4088

AN:

152010

Hom.:

183

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0945

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00786

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000279

Gnomad OTH

AF:

0.0187

GnomAD3 exomes

AF:

0.00701

AC:

1762

AN:

251272

Hom.:

AF XY:

0.00483

AC XY:

656

AN XY:

135782

show subpopulations

Gnomad AFR exome

AF:

0.0960

Gnomad AMR exome

AF:

0.00443

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000229

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000246

Gnomad OTH exome

AF:

0.00245

GnomAD4 exome

AF:

0.00271

AC:

3909

AN:

1442200

Hom.:

151

Cov.:

AF XY:

0.00230

AC XY:

1652

AN XY:

718804

show subpopulations

Gnomad4 AFR exome

AF:

0.0945

Gnomad4 AMR exome

AF:

0.00528

Gnomad4 ASJ exome

AF:

0.000154

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000291

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000146

Gnomad4 OTH exome

AF:

0.00557

GnomAD4 genome

AF:

0.0270

AC:

4100

AN:

152128

Hom.:

183

Cov.:

AF XY:

0.0256

AC XY:

1905

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.0945

Gnomad4 AMR

AF:

0.00779

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000279

Gnomad4 OTH

AF:

0.0185

Alfa

AF:

0.0200

Hom.:

Bravo

AF:

0.0300

Asia WGS

AF:

0.00404

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	Jun 27, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

3.9

DANN

Benign

0.84

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

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