2-27650459-C-G

Position:

• chr2-27650459-C-G

Variant summary

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

The NM_007266.4(GPN1):​c.*259C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 221,554 control chromosomes in the GnomAD database, including 7,788 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.23 (4886 hom., cov: 32)
  • Exomes 𝑓: 0.26 (2902 hom.)
• Consequence: GPN1 NM_007266.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0260

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]

SUPT7L (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.557 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPN1	NM_007266.4	c.*259C>G		3_prime_UTR_variant	14/14	ENST00000610189.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPN1	ENST00000610189.2	c.*259C>G		3_prime_UTR_variant	14/14	1	NM_007266.4	P1

Frequencies

GnomAD3 genomes AF: 0.230 AC: 35009 AN: 151992 Hom.: 4879 Cov.: 32

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.370

Gnomad AMR AF: 0.382

Gnomad ASJ AF: 0.206

Gnomad EAS AF: 0.574

Gnomad SAS AF: 0.318

Gnomad FIN AF: 0.231

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.243

GnomAD4 exome AF: 0.265 AC: 18402 AN: 69444 Hom.: 2902 Cov.: 0 AF XY: 0.265 AC XY: 9397 AN XY: 35480

Gnomad4 AFR exome AF: 0.137

Gnomad4 AMR exome AF: 0.428

Gnomad4 ASJ exome AF: 0.225

Gnomad4 EAS exome AF: 0.529

Gnomad4 SAS exome AF: 0.313

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.225

Gnomad4 OTH exome AF: 0.257

GnomAD4 genome AF: 0.230 AC: 35040 AN: 152110 Hom.: 4886 Cov.: 32 AF XY: 0.237 AC XY: 17647 AN XY: 74354

Gnomad4 AFR AF: 0.142

Gnomad4 AMR AF: 0.383

Gnomad4 ASJ AF: 0.206

Gnomad4 EAS AF: 0.574

Gnomad4 SAS AF: 0.318

Gnomad4 FIN AF: 0.231

Gnomad4 NFE AF: 0.217

Gnomad4 OTH AF: 0.242

Alfa AF: 0.223 Hom.: 552

Bravo AF: 0.243

Asia WGS AF: 0.434 AC: 1505 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.7
DANN	Benign	0.49

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: rs8731; hg19: chr2-27873326; COSMIC: COSV53112573; COSMIC: COSV53112573;