rs2736683

Variant names:

• chr8-63027580-T-A
• rs2736683
• NM_003878.3:c.276-315A>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.276-315A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 152,004 control chromosomes in the GnomAD database, including 4,240 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 0.21 (4240 hom., cov: 32)
• Consequence: GGH NM_003878.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.82
• Publications: 6 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 (SAS) allele frequency at 95% confidence interval = 0.323 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GGH	NM_003878.3	c.276-315A>T		intron_variant	Intron 3 of 8	ENST00000260118.7	NP_003869.1
GGH	NM_001410926.1	c.276-315A>T		intron_variant	Intron 3 of 7		NP_001397855.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GGH	ENST00000260118.7	c.276-315A>T		intron_variant	Intron 3 of 8	1	NM_003878.3	ENSP00000260118.6

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31773 AN: 151886 Hom.: 4232 Cov.: 32

Gnomad AFR AF: 0.0544

Gnomad AMI AF: 0.211

Gnomad AMR AF: 0.186

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.122

Gnomad SAS AF: 0.338

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.286

Gnomad OTH AF: 0.207

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

GnomAD4 genome AF: 0.209 AC: 31784 AN: 152004 Hom.: 4240 Cov.: 32 AF XY: 0.212 AC XY: 15736 AN XY: 74326

African (AFR) AF: 0.0543 AC: 2252 AN: 41508

American (AMR) AF: 0.186 AC: 2836 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.199 AC: 689 AN: 3464

East Asian (EAS) AF: 0.121 AC: 626 AN: 5170

South Asian (SAS) AF: 0.337 AC: 1625 AN: 4820

European-Finnish (FIN) AF: 0.342 AC: 3596 AN: 10528

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.286 AC: 19452 AN: 67938

Other (OTH) AF: 0.214 AC: 451 AN: 2104

Alfa AF: 0.259 Hom.: 683

Bravo AF: 0.186

Asia WGS AF: 0.233 AC: 808 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	12
DANN	Benign	0.84
PhyloP100		1.8
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: rs2736683; hg19: chr8-63940139;