chr8-63031785-G-A

Variant names:

• chr8-63031785-G-A
• rs17194931
• NM_003878.3:c.225-1568C>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.225-1568C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0712 in 152,222 control chromosomes in the GnomAD database, including 437 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 0.071 (437 hom., cov: 32)
• Consequence: GGH NM_003878.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.286
• Publications: 7 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]

ENSG00000310188 (HGNC:):

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 = 0.158 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.225-1568C>T		intron	N/A	NP_003869.1
	GGH	NM_001410926.1		c.225-1568C>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.225-1568C>T		intron	N/A	ENSP00000260118.6
	GGH	ENST00000518113.2	TSL:3	c.225-1568C>T		intron	N/A	ENSP00000504520.1
	GGH	ENST00000677482.1		c.225-1568C>T		intron	N/A	ENSP00000504590.1

Frequencies

GnomAD3 genomes AF: 0.0712 AC: 10832 AN: 152104 Hom.: 435 Cov.: 32

Gnomad AFR AF: 0.0275

Gnomad AMI AF: 0.0771

Gnomad AMR AF: 0.0504

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.0746

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.0588

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0946

Gnomad OTH AF: 0.0755

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

GnomAD4 genome AF: 0.0712 AC: 10831 AN: 152222 Hom.: 437 Cov.: 32 AF XY: 0.0710 AC XY: 5281 AN XY: 74416

African (AFR) AF: 0.0274 AC: 1139 AN: 41554

American (AMR) AF: 0.0502 AC: 768 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 424 AN: 3472

East Asian (EAS) AF: 0.0749 AC: 387 AN: 5164

South Asian (SAS) AF: 0.167 AC: 806 AN: 4818

European-Finnish (FIN) AF: 0.0588 AC: 623 AN: 10602

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0946 AC: 6431 AN: 68006

Other (OTH) AF: 0.0747 AC: 158 AN: 2114

Alfa AF: 0.0666 Hom.: 55

Bravo AF: 0.0676

Asia WGS AF: 0.114 AC: 401 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.0
DANN	Benign	0.50
PhyloP100		0.29
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: rs17194931; hg19: chr8-63944344;