rs13143848

Positions:

• chr4-99522563-G-A
• chr4-99522563-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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 same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.30 (7039 hom., cov: 31)
  • Exomes 𝑓: 0.30 (68722 hom.)
• Consequence: C4orf17 NM_032149.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.112

Genes affected

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

ACMG classification

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/exons	MANE	UniProt
C4orf17	NM_032149.3	c.191G>A	p.Gly64Glu	missense_variant	3/9	ENST00000326581.9
C4orf17	XM_011532315.3	c.191G>A	p.Gly64Glu	missense_variant	3/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C4orf17	ENST00000326581.9	c.191G>A	p.Gly64Glu	missense_variant	3/9	1	NM_032149.3	P2
C4orf17	ENST00000514652.5	c.191G>A	p.Gly64Glu	missense_variant	3/8	5		A2
C4orf17	ENST00000503257.1	n.188G>A		non_coding_transcript_exon_variant	2/4	5
C4orf17	ENST00000477187.1	c.191G>A	p.Gly64Glu	missense_variant, NMD_transcript_variant	3/10	2

Frequencies

GnomAD3 genomes AF: 0.300 AC: 45505 AN: 151706 Hom.: 7040 Cov.: 31

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

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.: 34 AF XY: 0.308 AC XY: 223552 AN XY: 726450

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.: 31 AF XY: 0.294 AC XY: 21847 AN XY: 74184

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	T
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	N
LIST_S2	Benign	0.38	T;T
MetaRNN	Benign	0.00088	T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.1	M;.
MutationTaster	Benign	1.0	P;P
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	T
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

Other links and lift over

dbSNP: rs13143848; hg19: chr4-100443720; COSMIC: COSV58511611;