rs10957267

Positions:

• chr8-63031692-T-A
• chr8-63031692-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000260118.7(GGH):​c.225-1475A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 152,176 control chromosomes in the GnomAD database, including 2,631 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 0.18 (2631 hom., cov: 32)
• Consequence: GGH ENST00000260118.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.179

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.399 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GGH	NM_003878.3	c.225-1475A>T		intron_variant		ENST00000260118.7	NP_003869.1
GGH	NM_001410926.1	c.225-1475A>T		intron_variant			NP_001397855.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GGH	ENST00000260118.7	c.225-1475A>T		intron_variant		1	NM_003878.3	ENSP00000260118	P1

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27318 AN: 152058 Hom.: 2622 Cov.: 32

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.207

Gnomad EAS AF: 0.413

Gnomad SAS AF: 0.270

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.171

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

GnomAD4 genome AF: 0.180 AC: 27349 AN: 152176 Hom.: 2631 Cov.: 32 AF XY: 0.183 AC XY: 13616 AN XY: 74410

Gnomad4 AFR AF: 0.159

Gnomad4 AMR AF: 0.214

Gnomad4 ASJ AF: 0.207

Gnomad4 EAS AF: 0.413

Gnomad4 SAS AF: 0.269

Gnomad4 FIN AF: 0.148

Gnomad4 NFE AF: 0.164

Gnomad4 OTH AF: 0.169

Alfa AF: 0.164 Hom.: 249

Bravo AF: 0.185

Asia WGS AF: 0.301 AC: 1050 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	4.3
DANN	Benign	0.74

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

Publications

LitVar

Other links and lift over

dbSNP: rs10957267; hg19: chr8-63944251;