chr8-63028580-G-A

Variant names:

• chr8-63028580-G-A
• rs3780127
• NM_003878.3:c.276-1315C>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.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
• Publications: 4 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=-0.92).
• 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.276-1315C>T		intron	N/A	NP_003869.1
	GGH	NM_001410926.1		c.276-1315C>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.276-1315C>T		intron	N/A	ENSP00000260118.6
	GGH	ENST00000523788.2	TSL:2	n.1889C>T		non_coding_transcript_exon	Exon 3 of 7
	GGH	ENST00000678069.1		n.1896C>T		non_coding_transcript_exon	Exon 3 of 8

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.167 AC: 1 AN: 6

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.0530 AC: 2198 AN: 41492

American (AMR) AF: 0.0536 AC: 819 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 424 AN: 3468

East Asian (EAS) AF: 0.0751 AC: 389 AN: 5178

South Asian (SAS) AF: 0.167 AC: 805 AN: 4812

European-Finnish (FIN) AF: 0.0591 AC: 625 AN: 10584

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0948 AC: 6442 AN: 67984

Other (OTH) AF: 0.0777 AC: 164 AN: 2110

Alfa AF: 0.0891 Hom.: 1117

Bravo AF: 0.0765

Asia WGS AF: 0.117 AC: 413 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.77
DANN	Benign	0.44
PhyloP100		-0.53
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: rs3780127; hg19: chr8-63941139;