14-44905544-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001017923.2(C14orf28):​c.927G>T​(p.Glu309Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00594 in 1,505,316 control chromosomes in the GnomAD database, including 445 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.030 ( 222 hom., cov: 32)
Exomes 𝑓: 0.0032 ( 223 hom. )

Consequence

C14orf28
NM_001017923.2 missense

Scores

17

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.81
Variant links:
Genes affected
C14orf28 (HGNC:19834): (chromosome 14 open reading frame 28)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0016608238).
BP6
Variant 14-44905544-G-T is Benign according to our data. Variant chr14-44905544-G-T is described in ClinVar as [Benign]. Clinvar id is 789639.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
C14orf28NM_001017923.2 linkc.927G>T p.Glu309Asp missense_variant Exon 5 of 5 ENST00000325192.8 NP_001017923.1 Q4W4Y0
C14orf28XM_011536408.1 linkc.447G>T p.Glu149Asp missense_variant Exon 4 of 4 XP_011534710.1
LOC101927418NR_110050.1 linkn.161+6213C>A intron_variant Intron 1 of 2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
C14orf28ENST00000325192.8 linkc.927G>T p.Glu309Asp missense_variant Exon 5 of 5 1 NM_001017923.2 ENSP00000326846.3 Q4W4Y0
C14orf28ENST00000557112.1 linkc.837G>T p.Glu279Asp missense_variant Exon 4 of 4 5 ENSP00000451791.1 G3V4G8
C14orf28ENST00000555826.5 linkn.1786G>T non_coding_transcript_exon_variant Exon 3 of 3 2
ENSG00000258949ENST00000555157.1 linkn.107+6213C>A intron_variant Intron 1 of 2 2

Frequencies

GnomAD3 genomes
AF:
0.0303
AC:
4607
AN:
151974
Hom.:
220
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.106
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00865
Gnomad ASJ
AF:
0.00289
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000621
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000265
Gnomad OTH
AF:
0.0191
GnomAD3 exomes
AF:
0.00776
AC:
1816
AN:
233896
Hom.:
92
AF XY:
0.00597
AC XY:
758
AN XY:
127038
show subpopulations
Gnomad AFR exome
AF:
0.106
Gnomad AMR exome
AF:
0.00550
Gnomad ASJ exome
AF:
0.00279
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000366
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000167
Gnomad OTH exome
AF:
0.00357
GnomAD4 exome
AF:
0.00318
AC:
4308
AN:
1353224
Hom.:
223
Cov.:
30
AF XY:
0.00274
AC XY:
1823
AN XY:
665252
show subpopulations
Gnomad4 AFR exome
AF:
0.109
Gnomad4 AMR exome
AF:
0.00655
Gnomad4 ASJ exome
AF:
0.00200
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000861
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000160
Gnomad4 OTH exome
AF:
0.00688
GnomAD4 genome
AF:
0.0304
AC:
4628
AN:
152092
Hom.:
222
Cov.:
32
AF XY:
0.0292
AC XY:
2168
AN XY:
74340
show subpopulations
Gnomad4 AFR
AF:
0.107
Gnomad4 AMR
AF:
0.00864
Gnomad4 ASJ
AF:
0.00289
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000622
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000265
Gnomad4 OTH
AF:
0.0189
Alfa
AF:
0.00498
Hom.:
59
Bravo
AF:
0.0339
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.000259
AC:
1
ESP6500AA
AF:
0.0947
AC:
417
ESP6500EA
AF:
0.000465
AC:
4
ExAC
AF:
0.00959
AC:
1164
Asia WGS
AF:
0.00780
AC:
27
AN:
3476

ClinVar

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

Submissions by phenotype

not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Dec 31, 2019
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.15
BayesDel_addAF
Benign
-0.68
T
BayesDel_noAF
Benign
-0.67
CADD
Benign
17
DANN
Benign
0.94
DEOGEN2
Benign
0.023
T;.
Eigen
Benign
-0.27
Eigen_PC
Benign
-0.066
FATHMM_MKL
Benign
0.73
D
LIST_S2
Benign
0.69
T;T
MetaRNN
Benign
0.0017
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
-0.20
N;.
PROVEAN
Benign
-1.6
N;N
REVEL
Benign
0.076
Sift
Benign
0.14
T;T
Sift4G
Benign
0.44
T;T
Polyphen
0.0010
B;.
Vest4
0.038
MutPred
0.21
Loss of methylation at K310 (P = 0.0601);.;
MVP
0.23
MPC
0.23
ClinPred
0.0099
T
GERP RS
3.8
Varity_R
0.11
gMVP
0.13

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs61742835; hg19: chr14-45374747; API