rs719236

Variant names:

• chr8-63039192-G-T
• rs719236
• ENST00000677327.1:n.216C>A

Variant summary

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

The ENST00000679326.1(GGH):​n.-424C>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 165,152 control chromosomes in the GnomAD database, including 1,044 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 0.11 (970 hom., cov: 33)
  • Exomes 𝑓: 0.10 (74 hom.)
• Consequence: GGH ENST00000679326.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.225
• Publications: 4 publications found

Genes affected

GGH (HGNC:4248): (gamma-glutamyl hydrolase) This gene catalyzes the hydrolysis of folylpoly-gamma-glutamates and antifolylpoly-gamma-glutamates by the removal of gamma-linked polyglutamates and glutamate. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.203 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000679326.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GGH	ENST00000677327.1		n.216C>A		non_coding_transcript_exon	Exon 1 of 8
	GGH	ENST00000679326.1		n.-424C>A		non_coding_transcript_exon	Exon 1 of 10	ENSP00000504262.1	A0A7I2YQQ3
	GGH	ENST00000679326.1		n.-424C>A		5_prime_UTR	Exon 1 of 10	ENSP00000504262.1	A0A7I2YQQ3

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16072 AN: 152158 Hom.: 970 Cov.: 33

Gnomad AFR AF: 0.0895

Gnomad AMI AF: 0.0461

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.214

Gnomad SAS AF: 0.0923

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.0882

Gnomad OTH AF: 0.130

GnomAD4 exome AF: 0.103 AC: 1321 AN: 12876 Hom.: 74 Cov.: 0 AF XY: 0.103 AC XY: 680 AN XY: 6580

African (AFR) AF: 0.102 AC: 62 AN: 610

American (AMR) AF: 0.188 AC: 55 AN: 292

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 57 AN: 488

East Asian (EAS) AF: 0.189 AC: 174 AN: 920

South Asian (SAS) AF: 0.107 AC: 12 AN: 112

European-Finnish (FIN) AF: 0.0800 AC: 71 AN: 888

Middle Eastern (MID) AF: 0.128 AC: 10 AN: 78

European-Non Finnish (NFE) AF: 0.0917 AC: 791 AN: 8630

Other (OTH) AF: 0.104 AC: 89 AN: 858

GnomAD4 genome AF: 0.106 AC: 16076 AN: 152276 Hom.: 970 Cov.: 33 AF XY: 0.109 AC XY: 8117 AN XY: 74446

African (AFR) AF: 0.0894 AC: 3715 AN: 41566

American (AMR) AF: 0.183 AC: 2799 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.118 AC: 411 AN: 3470

East Asian (EAS) AF: 0.214 AC: 1105 AN: 5166

South Asian (SAS) AF: 0.0928 AC: 447 AN: 4816

European-Finnish (FIN) AF: 0.116 AC: 1230 AN: 10614

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

European-Non Finnish (NFE) AF: 0.0883 AC: 6003 AN: 68020

Other (OTH) AF: 0.130 AC: 276 AN: 2116

Alfa AF: 0.0921 Hom.: 91

Bravo AF: 0.113

Asia WGS AF: 0.157 AC: 543 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	2.5
DANN	Benign	0.47
PhyloP100		-0.23
PromoterAI		0.0031	Neutral

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs719236;

hg19: chr8-63951751;