rs11995525

Variant names:

• chr8-63022429-G-A
• rs11995525
• NM_003878.3:c.697+1478C>T

Variant summary

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

The NM_003878.3(GGH):​c.697+1478C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 151,758 control chromosomes in the GnomAD database, including 6,308 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 0.28 (6308 hom., cov: 32)
• Consequence: GGH NM_003878.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.895
• Publications: 5 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.356 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GGH	NM_003878.3	c.697+1478C>T		intron_variant	Intron 7 of 8	ENST00000260118.7	NP_003869.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GGH	ENST00000260118.7	c.697+1478C>T		intron_variant	Intron 7 of 8	1	NM_003878.3	ENSP00000260118.6

Frequencies

GnomAD3 genomes AF: 0.283 AC: 42967 AN: 151638 Hom.: 6295 Cov.: 32

Gnomad AFR AF: 0.303

Gnomad AMI AF: 0.211

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.139

Gnomad SAS AF: 0.370

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.288

Gnomad OTH AF: 0.254

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

GnomAD4 genome AF: 0.283 AC: 43010 AN: 151758 Hom.: 6308 Cov.: 32 AF XY: 0.284 AC XY: 21025 AN XY: 74148

African (AFR) AF: 0.303 AC: 12531 AN: 41354

American (AMR) AF: 0.211 AC: 3219 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.230 AC: 796 AN: 3468

East Asian (EAS) AF: 0.138 AC: 716 AN: 5172

South Asian (SAS) AF: 0.370 AC: 1781 AN: 4816

European-Finnish (FIN) AF: 0.342 AC: 3573 AN: 10462

Middle Eastern (MID) AF: 0.252 AC: 73 AN: 290

European-Non Finnish (NFE) AF: 0.288 AC: 19577 AN: 67932

Other (OTH) AF: 0.262 AC: 552 AN: 2110

Alfa AF: 0.304 Hom.: 892

Bravo AF: 0.269

Asia WGS AF: 0.269 AC: 936 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.5
DANN	Benign	0.60
PhyloP100		0.90
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: rs11995525; hg19: chr8-63934988;