chr8-63017730-C-A

Variant names:

• chr8-63017730-C-A
• rs12677953
• NM_003878.3:c.698-100G>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.698-100G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 669,168 control chromosomes in the GnomAD database, including 6,498 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 0.12 (1387 hom., cov: 33)
  • Exomes 𝑓: 0.12 (5111 hom.)
• Consequence: GGH NM_003878.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.545
• Publications: 9 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.328 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GGH	NM_003878.3	c.698-100G>T		intron_variant	Intron 7 of 8	ENST00000260118.7	NP_003869.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GGH	ENST00000260118.7	c.698-100G>T		intron_variant	Intron 7 of 8	1	NM_003878.3	ENSP00000260118.6

Frequencies

GnomAD3 genomes AF: 0.125 AC: 18945 AN: 152036 Hom.: 1377 Cov.: 33

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.146

Gnomad AMR AF: 0.173

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.340

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0950

Gnomad OTH AF: 0.119

GnomAD4 exome AF: 0.120 AC: 62111 AN: 517014 Hom.: 5111 Cov.: 7 AF XY: 0.118 AC XY: 32198 AN XY: 272346

African (AFR) AF: 0.122 AC: 1500 AN: 12260

American (AMR) AF: 0.230 AC: 4565 AN: 19820

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 1473 AN: 13516

East Asian (EAS) AF: 0.357 AC: 10599 AN: 29666

South Asian (SAS) AF: 0.122 AC: 4624 AN: 37960

European-Finnish (FIN) AF: 0.145 AC: 5945 AN: 41094

Middle Eastern (MID) AF: 0.0540 AC: 186 AN: 3444

European-Non Finnish (NFE) AF: 0.0907 AC: 30113 AN: 332108

Other (OTH) AF: 0.114 AC: 3106 AN: 27146

GnomAD4 genome AF: 0.125 AC: 18964 AN: 152154 Hom.: 1387 Cov.: 33 AF XY: 0.130 AC XY: 9650 AN XY: 74376

African (AFR) AF: 0.123 AC: 5094 AN: 41518

American (AMR) AF: 0.174 AC: 2654 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 383 AN: 3472

East Asian (EAS) AF: 0.341 AC: 1761 AN: 5166

South Asian (SAS) AF: 0.132 AC: 638 AN: 4824

European-Finnish (FIN) AF: 0.149 AC: 1579 AN: 10570

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0950 AC: 6458 AN: 68000

Other (OTH) AF: 0.117 AC: 247 AN: 2114

Alfa AF: 0.0977 Hom.: 900

Bravo AF: 0.128

Asia WGS AF: 0.199 AC: 692 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.15
DANN	Benign	0.16
PhyloP100		-0.55
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: rs12677953; hg19: chr8-63930289;