rs2736676

Variant names:

• chr8-63039417-C-T
• rs2736676
• ENST00000677327.1:n.-10G>A

Variant summary

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

The ENST00000679326.1(GGH):​n.-649G>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.818 in 152,178 control chromosomes in the GnomAD database, including 51,478 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 0.82 (51478 hom., cov: 32)
• Consequence: GGH ENST00000679326.1 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.02
• 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=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.955 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.-10G>A		upstream_gene	N/A
	GGH	ENST00000679326.1		n.-649G>A		upstream_gene	N/A	ENSP00000504262.1	A0A7I2YQQ3

Frequencies

GnomAD3 genomes AF: 0.818 AC: 124323 AN: 152060 Hom.: 51411 Cov.: 32

Gnomad AFR AF: 0.927

Gnomad AMI AF: 0.729

Gnomad AMR AF: 0.829

Gnomad ASJ AF: 0.756

Gnomad EAS AF: 0.977

Gnomad SAS AF: 0.885

Gnomad FIN AF: 0.810

Gnomad MID AF: 0.750

Gnomad NFE AF: 0.738

Gnomad OTH AF: 0.806

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

GnomAD4 genome AF: 0.818 AC: 124450 AN: 152178 Hom.: 51478 Cov.: 32 AF XY: 0.824 AC XY: 61297 AN XY: 74394

African (AFR) AF: 0.927 AC: 38498 AN: 41544

American (AMR) AF: 0.829 AC: 12676 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.756 AC: 2624 AN: 3472

East Asian (EAS) AF: 0.977 AC: 5034 AN: 5152

South Asian (SAS) AF: 0.886 AC: 4270 AN: 4822

European-Finnish (FIN) AF: 0.810 AC: 8588 AN: 10602

Middle Eastern (MID) AF: 0.755 AC: 222 AN: 294

European-Non Finnish (NFE) AF: 0.738 AC: 50170 AN: 67984

Other (OTH) AF: 0.809 AC: 1706 AN: 2110

Alfa AF: 0.780 Hom.: 17026

Bravo AF: 0.824

Asia WGS AF: 0.924 AC: 3214 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.15
DANN	Benign	0.83
PhyloP100		-2.0

Splicing

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

Other links and lift over

dbSNP: rs2736676; hg19: chr8-63951976;