rs3780127

Positions:

• chr8-63028580-G-A
• chr8-63028580-G-C

Variant summary

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

The NM_003878.3(GGH):​c.276-1315C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0786 in 152,114 control chromosomes in the GnomAD database, including 481 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 0.079 (481 hom., cov: 32)
  • Exomes 𝑓: 0.17 (0 hom.)
• Consequence: GGH NM_003878.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.530

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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GGH	NM_003878.3	c.276-1315C>T		intron_variant		ENST00000260118.7
GGH	NM_001410926.1	c.276-1315C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GGH	ENST00000260118.7	c.276-1315C>T		intron_variant		1	NM_003878.3	P1

Frequencies

GnomAD3 genomes AF: 0.0786 AC: 11949 AN: 151990 Hom.: 478 Cov.: 32

Gnomad AFR AF: 0.0528

Gnomad AMI AF: 0.0768

Gnomad AMR AF: 0.0538

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.0748

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.0591

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0947

Gnomad OTH AF: 0.0785

GnomAD4 exome AF: 0.167 AC: 1 AN: 6 Hom.: 0 AF XY: 0.167 AC XY: 1 AN XY: 6

Gnomad4 NFE exome AF: 0.167

GnomAD4 genome AF: 0.0786 AC: 11962 AN: 152108 Hom.: 481 Cov.: 32 AF XY: 0.0784 AC XY: 5828 AN XY: 74332

Gnomad4 AFR AF: 0.0530

Gnomad4 AMR AF: 0.0536

Gnomad4 ASJ AF: 0.122

Gnomad4 EAS AF: 0.0751

Gnomad4 SAS AF: 0.167

Gnomad4 FIN AF: 0.0591

Gnomad4 NFE AF: 0.0948

Gnomad4 OTH AF: 0.0777

Alfa AF: 0.0907 Hom.: 915

Bravo AF: 0.0765

Asia WGS AF: 0.117 AC: 413 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.77
DANN	Benign	0.44

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: rs3780127; hg19: chr8-63941139;