chr6-31957103-G-A

Variant names:

• chr6-31957103-G-A
• rs403569
• NM_002904.6:c.76-93C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002904.6(NELFE):​c.76-93C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0974 in 1,130,108 control chromosomes in the GnomAD database, including 6,292 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 0.12 (1282 hom., cov: 33)
  • Exomes 𝑓: 0.094 (5010 hom.)
• Consequence: NELFE NM_002904.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.13
• Publications: 14 publications found

Genes affected

NELFE (HGNC:13974): (negative elongation factor complex member E) The protein encoded by this gene is part of a complex termed negative elongation factor (NELF) which represses RNA polymerase II transcript elongation. This protein bears similarity to nuclear RNA-binding proteins; however, it has not been demonstrated that this protein binds RNA. The protein contains a tract of alternating basic and acidic residues, largely arginine (R) and aspartic acid (D). The gene localizes to the major histocompatibility complex (MHC) class III region on chromosome 6. [provided by RefSeq, Jul 2008]

MIR1236 (HGNC:33925): (microRNA 1236) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.196 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NELFE	NM_002904.6	c.76-93C>T		intron_variant	Intron 2 of 10	ENST00000375429.8	NP_002895.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NELFE	ENST00000375429.8	c.76-93C>T		intron_variant	Intron 2 of 10	1	NM_002904.6	ENSP00000364578.3

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18104 AN: 152058 Hom.: 1282 Cov.: 33

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.0462

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.0573

Gnomad EAS AF: 0.0622

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.0577

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0908

Gnomad OTH AF: 0.132

GnomAD4 exome AF: 0.0941 AC: 91988 AN: 977932 Hom.: 5010 AF XY: 0.0953 AC XY: 47081 AN XY: 494262

African (AFR) AF: 0.190 AC: 4357 AN: 22964

American (AMR) AF: 0.0736 AC: 2396 AN: 32550

Ashkenazi Jewish (ASJ) AF: 0.0549 AC: 997 AN: 18164

East Asian (EAS) AF: 0.0731 AC: 2720 AN: 37208

South Asian (SAS) AF: 0.146 AC: 9497 AN: 64844

European-Finnish (FIN) AF: 0.0654 AC: 2512 AN: 38410

Middle Eastern (MID) AF: 0.0627 AC: 278 AN: 4432

European-Non Finnish (NFE) AF: 0.0904 AC: 64681 AN: 715732

Other (OTH) AF: 0.104 AC: 4550 AN: 43628

GnomAD4 genome AF: 0.119 AC: 18128 AN: 152176 Hom.: 1282 Cov.: 33 AF XY: 0.117 AC XY: 8700 AN XY: 74406

African (AFR) AF: 0.199 AC: 8267 AN: 41476

American (AMR) AF: 0.102 AC: 1559 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0573 AC: 199 AN: 3470

East Asian (EAS) AF: 0.0622 AC: 322 AN: 5178

South Asian (SAS) AF: 0.134 AC: 646 AN: 4828

European-Finnish (FIN) AF: 0.0577 AC: 612 AN: 10604

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0908 AC: 6176 AN: 68010

Other (OTH) AF: 0.131 AC: 277 AN: 2110

Alfa AF: 0.100 Hom.: 852

Bravo AF: 0.126

Asia WGS AF: 0.155 AC: 537 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.8
DANN	Benign	0.43
PhyloP100		-3.1
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: rs403569; hg19: chr6-31924880;