rs11545076

Variant names:

• chr8-63038892-A-C
• rs11545076
• ENST00000677327.1:n.516T>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000679326.1(GGH):​n.-124T>G 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 0.247 in 487,604 control chromosomes in the GnomAD database, including 15,498 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 0.25 (4751 hom., cov: 33)
  • Exomes 𝑓: 0.25 (10747 hom.)
• Consequence: GGH ENST00000679326.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.180
• Publications: 13 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.287 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
	GGH	NM_003878.3	MANE Select	c.-124T>G		upstream_gene	N/A	NP_003869.1	Q92820
	GGH	NM_001410926.1		c.-124T>G		upstream_gene	N/A	NP_001397855.1	A0A7I2V5X9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GGH	ENST00000677327.1		n.516T>G		non_coding_transcript_exon	Exon 1 of 8
	GGH	ENST00000679326.1		n.-124T>G		non_coding_transcript_exon	Exon 1 of 10	ENSP00000504262.1	A0A7I2YQQ3
	GGH	ENST00000679326.1		n.-124T>G		5_prime_UTR	Exon 1 of 10	ENSP00000504262.1	A0A7I2YQQ3

Frequencies

GnomAD3 genomes AF: 0.245 AC: 37232 AN: 151920 Hom.: 4742 Cov.: 33

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.341

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.278

Gnomad EAS AF: 0.202

Gnomad SAS AF: 0.299

Gnomad FIN AF: 0.257

Gnomad MID AF: 0.232

Gnomad NFE AF: 0.282

Gnomad OTH AF: 0.271

GnomAD4 exome AF: 0.247 AC: 83021 AN: 335572 Hom.: 10747 Cov.: 5 AF XY: 0.250 AC XY: 43872 AN XY: 175212

African (AFR) AF: 0.166 AC: 1353 AN: 8158

American (AMR) AF: 0.234 AC: 2016 AN: 8628

Ashkenazi Jewish (ASJ) AF: 0.274 AC: 2781 AN: 10146

East Asian (EAS) AF: 0.213 AC: 4972 AN: 23314

South Asian (SAS) AF: 0.239 AC: 4896 AN: 20474

European-Finnish (FIN) AF: 0.243 AC: 5940 AN: 24446

Middle Eastern (MID) AF: 0.225 AC: 337 AN: 1498

European-Non Finnish (NFE) AF: 0.255 AC: 55871 AN: 219360

Other (OTH) AF: 0.248 AC: 4855 AN: 19548

GnomAD4 genome AF: 0.245 AC: 37265 AN: 152032 Hom.: 4751 Cov.: 33 AF XY: 0.245 AC XY: 18246 AN XY: 74352

African (AFR) AF: 0.178 AC: 7391 AN: 41508

American (AMR) AF: 0.236 AC: 3606 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.278 AC: 964 AN: 3464

East Asian (EAS) AF: 0.203 AC: 1037 AN: 5118

South Asian (SAS) AF: 0.300 AC: 1449 AN: 4830

European-Finnish (FIN) AF: 0.257 AC: 2724 AN: 10596

Middle Eastern (MID) AF: 0.243 AC: 71 AN: 292

European-Non Finnish (NFE) AF: 0.282 AC: 19147 AN: 67920

Other (OTH) AF: 0.269 AC: 566 AN: 2104

Alfa AF: 0.251 Hom.: 607

Bravo AF: 0.242

Asia WGS AF: 0.259 AC: 901 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	16
DANN	Benign	0.81
PhyloP100		0.18
PromoterAI		0.039	Neutral
Mutation Taster		=300/0	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

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

Other links and lift over

dbSNP: rs11545076;

hg19: chr8-63951451;