chr6-31952179-T-C

Position:

• chr6-31952179-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_002904.6(NELFE):​c.*122A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0992 in 1,433,984 control chromosomes in the GnomAD database, including 7,990 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.12 (1239 hom., cov: 32)
  • Exomes 𝑓: 0.097 (6751 hom.)
• Consequence: NELFE NM_002904.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0240

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant 6-31952179-T-C is Benign according to our data. Variant chr6-31952179-T-C is described in ClinVar as [Benign]. Clinvar id is 1259467.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NELFE	NM_002904.6	c.*122A>G		3_prime_UTR_variant	11/11	ENST00000375429.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NELFE	ENST00000375429.8	c.*122A>G		3_prime_UTR_variant	11/11	1	NM_002904.6	P1

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17867 AN: 152068 Hom.: 1241 Cov.: 32

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.0461

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.0573

Gnomad EAS AF: 0.0623

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.0578

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0911

Gnomad OTH AF: 0.131

GnomAD4 exome AF: 0.0971 AC: 124428 AN: 1281798 Hom.: 6751 Cov.: 19 AF XY: 0.0980 AC XY: 62976 AN XY: 642444

Gnomad4 AFR exome AF: 0.190

Gnomad4 AMR exome AF: 0.0742

Gnomad4 ASJ exome AF: 0.0560

Gnomad4 EAS exome AF: 0.0740

Gnomad4 SAS exome AF: 0.149

Gnomad4 FIN exome AF: 0.0650

Gnomad4 NFE exome AF: 0.0941

Gnomad4 OTH exome AF: 0.108

GnomAD4 genome AF: 0.118 AC: 17888 AN: 152186 Hom.: 1239 Cov.: 32 AF XY: 0.115 AC XY: 8584 AN XY: 74422

Gnomad4 AFR AF: 0.193

Gnomad4 AMR AF: 0.102

Gnomad4 ASJ AF: 0.0573

Gnomad4 EAS AF: 0.0623

Gnomad4 SAS AF: 0.133

Gnomad4 FIN AF: 0.0578

Gnomad4 NFE AF: 0.0911

Gnomad4 OTH AF: 0.130

Alfa AF: 0.0974 Hom.: 634

Bravo AF: 0.124

Asia WGS AF: 0.154 AC: 535 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	15
DANN	Benign	0.86

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: rs760070; hg19: chr6-31919956; COSMIC: COSV105306646; COSMIC: COSV105306646;