rs2273359

chr20-58987047-C-Gchr20-58987047-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198976.4(NELFCD):c.286+184C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0427 in 535,328 control chromosomes in the GnomAD database, including 569 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.041 (160 hom., cov: 32)
  • Exomes 𝑓: 0.043 (409 hom.)
• Consequence: NELFCD NM_198976.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.211

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]

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.077 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NELFCD	NM_198976.4	c.286+184C>G		intron_variant		ENST00000652272.2
NELFCD	XM_047440188.1	c.340+184C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NELFCD	ENST00000652272.2	c.286+184C>G		intron_variant			NM_198976.4	P1

Frequencies

GnomAD3 genomes AF: 0.0411 AC: 6244 AN: 152012 Hom.: 158 Cov.: 32

Gnomad AFR AF: 0.0286

Gnomad AMI AF: 0.0976

Gnomad AMR AF: 0.0698

Gnomad ASJ AF: 0.0432

Gnomad EAS AF: 0.0348

Gnomad SAS AF: 0.0834

Gnomad FIN AF: 0.0290

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0404

Gnomad OTH AF: 0.0478

GnomAD4 exome AF: 0.0434 AC: 16618 AN: 383198 Hom.: 409 Cov.: 4 AF XY: 0.0461 AC XY: 9274 AN XY: 201176

Gnomad4 AFR exome AF: 0.0262

Gnomad4 AMR exome AF: 0.0765

Gnomad4 ASJ exome AF: 0.0386

Gnomad4 EAS exome AF: 0.0322

Gnomad4 SAS exome AF: 0.0861

Gnomad4 FIN exome AF: 0.0250

Gnomad4 NFE exome AF: 0.0402

Gnomad4 OTH exome AF: 0.0410

GnomAD4 genome AF: 0.0411 AC: 6255 AN: 152130 Hom.: 160 Cov.: 32 AF XY: 0.0423 AC XY: 3143 AN XY: 74378

Gnomad4 AFR AF: 0.0286

Gnomad4 AMR AF: 0.0699

Gnomad4 ASJ AF: 0.0432

Gnomad4 EAS AF: 0.0351

Gnomad4 SAS AF: 0.0837

Gnomad4 FIN AF: 0.0290

Gnomad4 NFE AF: 0.0403

Gnomad4 OTH AF: 0.0511

Alfa AF: 0.0118 Hom.: 4

Bravo AF: 0.0420

Asia WGS AF: 0.0720 AC: 248 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
Cadd	Benign	9.3
Dann	Benign	0.75

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

Other links and lift over

dbSNP: rs2273359; hg19: chr20-57562102;