chr8-63037353-G-A

Variant names:

• chr8-63037353-G-A
• rs3780126
• NM_003878.3:c.109+1307C>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.109+1307C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.448 in 151,818 control chromosomes in the GnomAD database, including 15,743 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 0.45 (15743 hom., cov: 30)
• Consequence: GGH NM_003878.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.456
• Publications: 14 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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.569 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003878.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GGH	NM_003878.3	MANE Select	c.109+1307C>T		intron	N/A	NP_003869.1
	GGH	NM_001410926.1		c.109+1307C>T		intron	N/A	NP_001397855.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GGH	ENST00000260118.7	TSL:1 MANE Select	c.109+1307C>T		intron	N/A	ENSP00000260118.6
	GGH	ENST00000518113.2	TSL:3	c.109+1307C>T		intron	N/A	ENSP00000504520.1
	GGH	ENST00000677482.1		c.109+1307C>T		intron	N/A	ENSP00000504590.1

Frequencies

GnomAD3 genomes AF: 0.448 AC: 67901 AN: 151698 Hom.: 15718 Cov.: 30

Gnomad AFR AF: 0.575

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.424

Gnomad ASJ AF: 0.379

Gnomad EAS AF: 0.356

Gnomad SAS AF: 0.478

Gnomad FIN AF: 0.464

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.384

Gnomad OTH AF: 0.431

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

GnomAD4 genome AF: 0.448 AC: 67968 AN: 151818 Hom.: 15743 Cov.: 30 AF XY: 0.450 AC XY: 33386 AN XY: 74170

African (AFR) AF: 0.575 AC: 23779 AN: 41368

American (AMR) AF: 0.424 AC: 6472 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.379 AC: 1314 AN: 3468

East Asian (EAS) AF: 0.355 AC: 1825 AN: 5138

South Asian (SAS) AF: 0.478 AC: 2302 AN: 4816

European-Finnish (FIN) AF: 0.464 AC: 4889 AN: 10548

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.384 AC: 26093 AN: 67910

Other (OTH) AF: 0.438 AC: 921 AN: 2104

Alfa AF: 0.402 Hom.: 38938

Bravo AF: 0.448

Asia WGS AF: 0.440 AC: 1530 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.8
DANN	Benign	0.81
PhyloP100		-0.46
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: rs3780126; hg19: chr8-63949912;