rs3780130

Variant names:

• chr8-63028217-T-A
• rs3780130
• NM_003878.3:c.276-952A>T

Your query was ambiguous. Multiple possible variants found:

• chr8-63028217-T-A
• chr8-63028217-T-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003878.3(GGH):​c.276-952A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 151,896 control chromosomes in the GnomAD database, including 3,447 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 0.20 (3447 hom., cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GGH NM_003878.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0100
• 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.406 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.276-952A>T		intron	N/A	NP_003869.1
	GGH	NM_001410926.1		c.276-952A>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.276-952A>T		intron	N/A	ENSP00000260118.6
	GGH	ENST00000523479.1	TSL:5	n.269A>T		non_coding_transcript_exon	Exon 1 of 2
	GGH	ENST00000523788.2	TSL:2	n.2252A>T		non_coding_transcript_exon	Exon 3 of 7

Frequencies

GnomAD3 genomes AF: 0.202 AC: 30672 AN: 151776 Hom.: 3447 Cov.: 31

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.328

Gnomad ASJ AF: 0.224

Gnomad EAS AF: 0.422

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.312

Gnomad NFE AF: 0.194

Gnomad OTH AF: 0.264

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

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) AC: 0 AN: 0

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.202 AC: 30685 AN: 151896 Hom.: 3447 Cov.: 31 AF XY: 0.204 AC XY: 15130 AN XY: 74222

African (AFR) AF: 0.148 AC: 6151 AN: 41446

American (AMR) AF: 0.328 AC: 4985 AN: 15208

Ashkenazi Jewish (ASJ) AF: 0.224 AC: 776 AN: 3464

East Asian (EAS) AF: 0.421 AC: 2162 AN: 5132

South Asian (SAS) AF: 0.201 AC: 966 AN: 4810

European-Finnish (FIN) AF: 0.149 AC: 1571 AN: 10546

Middle Eastern (MID) AF: 0.312 AC: 91 AN: 292

European-Non Finnish (NFE) AF: 0.194 AC: 13175 AN: 67976

Other (OTH) AF: 0.263 AC: 556 AN: 2112

Alfa AF: 0.0911 Hom.: 128

Bravo AF: 0.219

Asia WGS AF: 0.306 AC: 1060 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.8
DANN	Benign	0.84
PhyloP100		-0.010
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3780130; hg19: chr8-63940776;