chr6-31958823-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_002904.6(NELFE):​c.-9+69G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0306 in 659,354 control chromosomes in the GnomAD database, including 655 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.031 ( 161 hom., cov: 33)
Exomes 𝑓: 0.030 ( 494 hom. )

Consequence

NELFE
NM_002904.6 intron

Scores

2

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.258

Publications

8 publications found
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.73).
BP6
Variant 6-31958823-C-T is Benign according to our data. Variant chr6-31958823-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 356299.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0308 (4686/152308) while in subpopulation NFE AF = 0.0361 (2454/68034). AF 95% confidence interval is 0.0349. There are 161 homozygotes in GnomAd4. There are 2575 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
BS2
High Homozygotes in GnomAd4 at 161 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NELFENM_002904.6 linkc.-9+69G>A intron_variant Intron 1 of 10 ENST00000375429.8 NP_002895.3 P18615-1A0A1U9X830

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NELFEENST00000375429.8 linkc.-9+69G>A intron_variant Intron 1 of 10 1 NM_002904.6 ENSP00000364578.3 P18615-1

Frequencies

GnomAD3 genomes
AF:
0.0308
AC:
4686
AN:
152190
Hom.:
161
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00627
Gnomad AMI
AF:
0.0857
Gnomad AMR
AF:
0.0124
Gnomad ASJ
AF:
0.00173
Gnomad EAS
AF:
0.000962
Gnomad SAS
AF:
0.0122
Gnomad FIN
AF:
0.150
Gnomad MID
AF:
0.0158
Gnomad NFE
AF:
0.0361
Gnomad OTH
AF:
0.0177
GnomAD4 exome
AF:
0.0305
AC:
15464
AN:
507046
Hom.:
494
Cov.:
0
AF XY:
0.0290
AC XY:
7917
AN XY:
273324
show subpopulations
African (AFR)
AF:
0.00545
AC:
77
AN:
14122
American (AMR)
AF:
0.00955
AC:
264
AN:
27652
Ashkenazi Jewish (ASJ)
AF:
0.00304
AC:
51
AN:
16750
East Asian (EAS)
AF:
0.000189
AC:
6
AN:
31746
South Asian (SAS)
AF:
0.00955
AC:
537
AN:
56244
European-Finnish (FIN)
AF:
0.130
AC:
4121
AN:
31726
Middle Eastern (MID)
AF:
0.00809
AC:
30
AN:
3708
European-Non Finnish (NFE)
AF:
0.0328
AC:
9717
AN:
296530
Other (OTH)
AF:
0.0231
AC:
661
AN:
28568
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.513
Heterozygous variant carriers
0
828
1656
2483
3311
4139
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
36
72
108
144
180
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.0308
AC:
4686
AN:
152308
Hom.:
161
Cov.:
33
AF XY:
0.0346
AC XY:
2575
AN XY:
74464
show subpopulations
African (AFR)
AF:
0.00626
AC:
260
AN:
41566
American (AMR)
AF:
0.0124
AC:
190
AN:
15308
Ashkenazi Jewish (ASJ)
AF:
0.00173
AC:
6
AN:
3472
East Asian (EAS)
AF:
0.000964
AC:
5
AN:
5186
South Asian (SAS)
AF:
0.0124
AC:
60
AN:
4832
European-Finnish (FIN)
AF:
0.150
AC:
1592
AN:
10592
Middle Eastern (MID)
AF:
0.0136
AC:
4
AN:
294
European-Non Finnish (NFE)
AF:
0.0361
AC:
2454
AN:
68034
Other (OTH)
AF:
0.0175
AC:
37
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.497
Heterozygous variant carriers
0
226
452
677
903
1129
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
58
116
174
232
290
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.0303
Hom.:
110
Bravo
AF:
0.0191
Asia WGS
AF:
0.00375
AC:
13
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Trichohepatoenteric syndrome Benign:1
Jun 14, 2016
Illumina Laboratory Services, Illumina
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

not provided Benign:1
-
Breakthrough Genomics, Breakthrough Genomics
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.73
CADD
Benign
7.5
DANN
Benign
0.86
PhyloP100
0.26
PromoterAI
-0.063
Neutral
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0
Mutation Taster
=300/0
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

Publications

Other links and lift over

dbSNP: rs17201466; hg19: chr6-31926600; API