rs3749147

Variant names:

• chr2-27629051-G-A
• rs3749147
• ENST00000264718.7:c.35G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-27629051-G-A
• chr2-27629051-G-C
• chr2-27629051-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000264718.7(GPN1):​c.35G>A​(p.Arg12Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 1,613,938 control chromosomes in the GnomAD database, including 50,452 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.20 (3790 hom., cov: 32)
  • Exomes 𝑓: 0.25 (46662 hom.)
• Consequence: GPN1 ENST00000264718.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.742
• Publications: 58 publications found

Genes affected

GPN1 (HGNC:17030): (GPN-loop GTPase 1) This gene encodes a guanosine triphosphatase enzyme. The encoded protein may play a role in DNA repair and may function in activation of transcription. Alternatively spliced transcript variants have been described. [provided by RefSeq, Feb 2009]

ENSG00000259080 (HGNC:):

CCDC121 (HGNC:25833): (coiled-coil domain containing 121)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0043020844).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.295 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000264718.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPN1	NM_007266.4	MANE Select	c.-8G>A		5_prime_UTR	Exon 1 of 14	NP_009197.3	Q9HCN4-1
	GPN1	NM_001145047.2		c.8-324G>A		intron	N/A	NP_001138519.1	Q9HCN4-4
	GPN1	NM_001145048.2		c.-127+337G>A		intron	N/A	NP_001138520.1	Q9HCN4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPN1	ENST00000264718.7	TSL:1	c.35G>A	p.Arg12Lys	missense	Exon 1 of 14	ENSP00000264718.3	Q9HCN4-5
	GPN1	ENST00000616939.4	TSL:1	c.35G>A	p.Arg12Lys	missense	Exon 1 of 14	ENSP00000484680.1	Q9HCN4-5
	GPN1	ENST00000610189.2	TSL:1 MANE Select	c.-8G>A		5_prime_UTR	Exon 1 of 14	ENSP00000476446.1	Q9HCN4-1

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30876 AN: 152098 Hom.: 3791 Cov.: 32

Gnomad AFR AF: 0.0642

Gnomad AMI AF: 0.193

Gnomad AMR AF: 0.203

Gnomad ASJ AF: 0.345

Gnomad EAS AF: 0.307

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.258

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.264

Gnomad OTH AF: 0.250

GnomAD2 exomes AF: 0.229 AC: 57492 AN: 251142 AF XY: 0.234

Gnomad AFR exome AF: 0.0576

Gnomad AMR exome AF: 0.139

Gnomad ASJ exome AF: 0.345

Gnomad EAS exome AF: 0.309

Gnomad FIN exome AF: 0.254

Gnomad NFE exome AF: 0.263

Gnomad OTH exome AF: 0.257

GnomAD4 exome AF: 0.247 AC: 361611 AN: 1461722 Hom.: 46662 Cov.: 37 AF XY: 0.247 AC XY: 179937 AN XY: 727168

African (AFR) AF: 0.0559 AC: 1871 AN: 33478

American (AMR) AF: 0.144 AC: 6441 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.342 AC: 8938 AN: 26134

East Asian (EAS) AF: 0.348 AC: 13826 AN: 39686

South Asian (SAS) AF: 0.187 AC: 16138 AN: 86250

European-Finnish (FIN) AF: 0.249 AC: 13279 AN: 53380

Middle Eastern (MID) AF: 0.315 AC: 1815 AN: 5766

European-Non Finnish (NFE) AF: 0.256 AC: 284142 AN: 1111922

Other (OTH) AF: 0.251 AC: 15161 AN: 60392

GnomAD4 genome AF: 0.203 AC: 30872 AN: 152216 Hom.: 3790 Cov.: 32 AF XY: 0.203 AC XY: 15136 AN XY: 74420

African (AFR) AF: 0.0640 AC: 2660 AN: 41566

American (AMR) AF: 0.203 AC: 3107 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.345 AC: 1199 AN: 3472

East Asian (EAS) AF: 0.307 AC: 1586 AN: 5164

South Asian (SAS) AF: 0.179 AC: 864 AN: 4822

European-Finnish (FIN) AF: 0.258 AC: 2729 AN: 10594

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.264 AC: 17923 AN: 67990

Other (OTH) AF: 0.252 AC: 531 AN: 2106

Alfa AF: 0.244 Hom.: 17242

Bravo AF: 0.192

TwinsUK AF: 0.251 AC: 931

ALSPAC AF: 0.249 AC: 961

ESP6500AA AF: 0.0663 AC: 292

ESP6500EA AF: 0.265 AC: 2283

ExAC AF: 0.225 AC: 27292

Asia WGS AF: 0.202 AC: 703 AN: 3478

EpiCase AF: 0.287

EpiControl AF: 0.287

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.68	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	15
DANN	Benign	0.91
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.027	N
LIST_S2	Benign	0.41	T
MetaRNN	Benign	0.0043	T
MetaSVM	Benign	-0.96	T
PhyloP100		0.74
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	0.040	N
REVEL	Benign	0.031
Sift	Benign	0.63	T
Sift4G	Benign	0.90	T
Vest4		0.11
MPC		0.21
ClinPred		0.0038	T
GERP RS		1.9
PromoterAI		0.078	Neutral
gMVP		0.49
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3749147; hg19: chr2-27851918; COSMIC: COSV53112445; COSMIC: COSV53112445;