rs2273359

Variant names:

• chr20-58987047-C-G
• rs2273359
• NM_198976.4:c.286+184C>G

Your query was ambiguous. Multiple possible variants found:

• chr20-58987047-C-G
• chr20-58987047-C-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 15 publications found

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

Our verdict: Benign. The variant received -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NELFCD	NM_198976.4	MANE Select	c.286+184C>G		intron	N/A	NP_945327.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NELFCD	ENST00000652272.2	MANE Select	c.286+184C>G		intron	N/A	ENSP00000499018.1
	NELFCD	ENST00000602795.6	TSL:1	c.340+184C>G		intron	N/A	ENSP00000473290.1
	NELFCD	ENST00000460601.5	TSL:1	n.319+184C>G		intron	N/A	ENSP00000436783.2

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

African (AFR) AF: 0.0262 AC: 245 AN: 9362

American (AMR) AF: 0.0765 AC: 836 AN: 10932

Ashkenazi Jewish (ASJ) AF: 0.0386 AC: 473 AN: 12242

East Asian (EAS) AF: 0.0322 AC: 809 AN: 25154

South Asian (SAS) AF: 0.0861 AC: 2934 AN: 34082

European-Finnish (FIN) AF: 0.0250 AC: 701 AN: 28058

Middle Eastern (MID) AF: 0.0472 AC: 86 AN: 1822

European-Non Finnish (NFE) AF: 0.0402 AC: 9598 AN: 238722

Other (OTH) AF: 0.0410 AC: 936 AN: 22824

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

African (AFR) AF: 0.0286 AC: 1185 AN: 41500

American (AMR) AF: 0.0699 AC: 1069 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0432 AC: 150 AN: 3470

East Asian (EAS) AF: 0.0351 AC: 182 AN: 5182

South Asian (SAS) AF: 0.0837 AC: 403 AN: 4814

European-Finnish (FIN) AF: 0.0290 AC: 306 AN: 10562

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0403 AC: 2743 AN: 68000

Other (OTH) AF: 0.0511 AC: 108 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	9.3
DANN	Benign	0.75
PhyloP100		0.21
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2273359; hg19: chr20-57562102;