dbSNP rs13143848: C4orf17:p.Gly64Glu (chr4-99522563-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_032149.3(C4orf17):c.191G>A(p.Gly64Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 1,611,828 control chromosomes in the GnomAD database, including 75,761 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.30 ( 7039 hom., cov: 31)

Exomes 𝑓: 0.30 ( 68722 hom. )

Consequence

C4orf17
NM_032149.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.112

Variant links:

Genes affected

C4orf17 (HGNC:25274): (chromosome 4 open reading frame 17)

C4orf17 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=8.7961555E-4).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.398 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C4orf17	NM_032149.3 link	c.191G>A	p.Gly64Glu	missense_variant	Exon 3 of 9	ENST00000326581.9	NP_115525.2	Q53FE4-1
C4orf17	XM_011532315.3 link	c.191G>A	p.Gly64Glu	missense_variant	Exon 3 of 6		XP_011530617.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
C4orf17	ENST00000326581.9 link	c.191G>A	p.Gly64Glu	missense_variant	Exon 3 of 9	1	NM_032149.3	ENSP00000322582.4	Q53FE4-1
C4orf17	ENST00000514652.5 link	c.191G>A	p.Gly64Glu	missense_variant	Exon 3 of 8	5		ENSP00000427663.1	D6RHU4
C4orf17	ENST00000477187.1 link	n.191G>A		non_coding_transcript_exon_variant	Exon 3 of 10	2		ENSP00000423411.1	Q53FE4-2
C4orf17	ENST00000503257.1 link	n.188G>A		non_coding_transcript_exon_variant	Exon 2 of 4	5

Frequencies

GnomAD3 genomes

AF:

0.300

AC:

45505

AN:

151706

Hom.:

7040

Cov.:

show subpopulations

Gnomad AFR

AF:

0.331

Gnomad AMI

AF:

0.269

Gnomad AMR

AF:

0.263

Gnomad ASJ

AF:

0.355

Gnomad EAS

AF:

0.200

Gnomad SAS

AF:

0.415

Gnomad FIN

AF:

0.199

Gnomad MID

AF:

0.392

Gnomad NFE

AF:

0.301

Gnomad OTH

AF:

0.341

GnomAD3 exomes

AF:

0.290

AC:

72914

AN:

251060

Hom.:

11360

AF XY:

0.302

AC XY:

40983

AN XY:

135672

show subpopulations

Gnomad AFR exome

AF:

0.335

Gnomad AMR exome

AF:

0.198

Gnomad ASJ exome

AF:

0.346

Gnomad EAS exome

AF:

0.198

Gnomad SAS exome

AF:

0.418

Gnomad FIN exome

AF:

0.200

Gnomad NFE exome

AF:

0.305

Gnomad OTH exome

AF:

0.299

GnomAD4 exome

AF:

0.303

AC:

441697

AN:

1460004

Hom.:

68722

Cov.:

AF XY:

0.308

AC XY:

223552

AN XY:

726450

show subpopulations

Gnomad4 AFR exome

AF:

0.332

Gnomad4 AMR exome

AF:

0.208

Gnomad4 ASJ exome

AF:

0.352

Gnomad4 EAS exome

AF:

0.176

Gnomad4 SAS exome

AF:

0.421

Gnomad4 FIN exome

AF:

0.200

Gnomad4 NFE exome

AF:

0.304

Gnomad4 OTH exome

AF:

0.305

GnomAD4 genome

AF:

0.300

AC:

45519

AN:

151824

Hom.:

7039

Cov.:

AF XY:

0.294

AC XY:

21847

AN XY:

74184

show subpopulations

Gnomad4 AFR

AF:

0.330

Gnomad4 AMR

AF:

0.263

Gnomad4 ASJ

AF:

0.355

Gnomad4 EAS

AF:

0.200

Gnomad4 SAS

AF:

0.413

Gnomad4 FIN

AF:

0.199

Gnomad4 NFE

AF:

0.301

Gnomad4 OTH

AF:

0.340

Alfa

AF:

0.307

Hom.:

18327

Bravo

AF:

0.301

TwinsUK

AF:

0.302

AC:

1118

ALSPAC

AF:

0.317

AC:

1222

ESP6500AA

AF:

0.336

AC:

1479

ESP6500EA

AF:

0.308

AC:

2649

ExAC

AF:

0.297

AC:

36117

Asia WGS

AF:

0.334

AC:

1162

AN:

3478

EpiCase

AF:

0.319

EpiControl

AF:

0.328

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.72

CADD

Benign

1.5

DANN

Benign

0.48

DEOGEN2

Benign

0.0040

T;.

Eigen

Benign

-0.82

Eigen_PC

Benign

-0.89

FATHMM_MKL

Benign

0.016

LIST_S2

Benign

0.38

T;T

MetaRNN

Benign

0.00088

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Uncertain

2.1

M;.

PROVEAN

Benign

-1.4

N;N

REVEL

Benign

0.040

Sift

Benign

0.38

T;T

Sift4G

Benign

0.18

T;T

Polyphen

0.23

B;.

Vest4

0.071

MPC

0.15

ClinPred

0.0021

GERP RS

1.2

Varity_R

0.038

gMVP

0.21

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over