chr8-63039447-G-A

Variant names:

• chr8-63039447-G-A
• rs3758147
• ENST00000677327.1:n.-40C>T

Variant summary

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

The ENST00000679326.1(GGH):​n.-679C>T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0797 in 152,252 control chromosomes in the GnomAD database, including 915 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 0.080 (915 hom., cov: 33)
• Consequence: GGH ENST00000679326.1 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.699
• Publications: 2 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=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.403 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.-40C>T		upstream_gene	N/A
	GGH	ENST00000679326.1		n.-679C>T		upstream_gene	N/A	ENSP00000504262.1	A0A7I2YQQ3

Frequencies

GnomAD3 genomes AF: 0.0797 AC: 12124 AN: 152134 Hom.: 908 Cov.: 33

Gnomad AFR AF: 0.0222

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.0841

Gnomad EAS AF: 0.417

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.0898

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0699

Gnomad OTH AF: 0.0708

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0797 AC: 12131 AN: 152252 Hom.: 915 Cov.: 33 AF XY: 0.0846 AC XY: 6302 AN XY: 74448

African (AFR) AF: 0.0222 AC: 921 AN: 41560

American (AMR) AF: 0.150 AC: 2289 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0841 AC: 292 AN: 3472

East Asian (EAS) AF: 0.418 AC: 2154 AN: 5158

South Asian (SAS) AF: 0.105 AC: 506 AN: 4820

European-Finnish (FIN) AF: 0.0898 AC: 953 AN: 10616

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0698 AC: 4749 AN: 68014

Other (OTH) AF: 0.0696 AC: 147 AN: 2112

Alfa AF: 0.0638 Hom.: 230

Bravo AF: 0.0845

Asia WGS AF: 0.210 AC: 728 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	8.1
DANN	Benign	0.84
PhyloP100		0.70

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: rs3758147;

hg19: chr8-63952006;