2-27650459-C-G

Variant names:

• chr2-27650459-C-G
• rs8731
• NM_007266.4:c.*259C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 16 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]

SUPT7L (HGNC:30632): (SPT7 like, STAGA complex subunit gamma) SUPT7L is a protein subunit of the human STAGA complex (SPT3; (MIM 602947)/TAF9 (MIM 600822)/GCN5 (MIM 602301) acetyltransferase complex), which is a chromatin-modifying multiprotein complex (Martinez et al., 2001 [PubMed 11564863]).[supplied by OMIM, Apr 2009]

SUPT7L Gene-Disease associations (from GenCC):

• lipodystrophy

  Inheritance: AR Classification: LIMITED Submitted by: PanelApp Australia, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007266.4. 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.*259C>G		3_prime_UTR	Exon 14 of 14	NP_009197.3	Q9HCN4-1
	GPN1	NM_001145047.2		c.*259C>G		3_prime_UTR	Exon 15 of 15	NP_001138519.1	Q9HCN4-4
	GPN1	NM_001145048.2		c.*259C>G		3_prime_UTR	Exon 14 of 14	NP_001138520.1	Q9HCN4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPN1	ENST00000610189.2	TSL:1 MANE Select	c.*259C>G		3_prime_UTR	Exon 14 of 14	ENSP00000476446.1	Q9HCN4-1
	GPN1	ENST00000264718.7	TSL:1	c.*259C>G		3_prime_UTR	Exon 14 of 14	ENSP00000264718.3	Q9HCN4-5
	GPN1	ENST00000616939.4	TSL:1	c.*259C>G		3_prime_UTR	Exon 14 of 14	ENSP00000484680.1	Q9HCN4-5

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

African (AFR) AF: 0.137 AC: 314 AN: 2300

American (AMR) AF: 0.428 AC: 1283 AN: 2996

Ashkenazi Jewish (ASJ) AF: 0.225 AC: 591 AN: 2622

East Asian (EAS) AF: 0.529 AC: 3214 AN: 6076

South Asian (SAS) AF: 0.313 AC: 1072 AN: 3420

European-Finnish (FIN) AF: 0.250 AC: 920 AN: 3678

Middle Eastern (MID) AF: 0.178 AC: 53 AN: 298

European-Non Finnish (NFE) AF: 0.225 AC: 9801 AN: 43566

Other (OTH) AF: 0.257 AC: 1154 AN: 4488

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

African (AFR) AF: 0.142 AC: 5897 AN: 41524

American (AMR) AF: 0.383 AC: 5850 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.206 AC: 715 AN: 3468

East Asian (EAS) AF: 0.574 AC: 2972 AN: 5174

South Asian (SAS) AF: 0.318 AC: 1535 AN: 4820

European-Finnish (FIN) AF: 0.231 AC: 2443 AN: 10558

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.217 AC: 14732 AN: 67970

Other (OTH) AF: 0.242 AC: 511 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.7
DANN	Benign	0.49
PhyloP100		0.026
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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