rs1923934

chr10-87090397-G-Achr10-87090397-G-Cchr10-87090397-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005271.5(GLUD1):c.445+3928C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 152,000 control chromosomes in the GnomAD database, including 6,631 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 0.28 (6631 hom., cov: 32)
• Consequence: GLUD1 NM_005271.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.349

Genes affected

GLUD1 (HGNC:4335): (glutamate dehydrogenase 1) This gene encodes glutamate dehydrogenase, which is a mitochondrial matrix enzyme that catalyzes the oxidative deamination of glutamate to alpha-ketoglutarate and ammonia. This enzyme has an important role in regulating amino acid-induced insulin secretion. It is allosterically activated by ADP and inhibited by GTP and ATP. Activating mutations in this gene are a common cause of congenital hyperinsulinism. Alternative splicing of this gene results in multiple transcript variants. The related glutamate dehydrogenase 2 gene on the human X-chromosome originated from this gene via retrotransposition and encodes a soluble form of glutamate dehydrogenase. Related pseudogenes have been identified on chromosomes 10, 18 and X. [provided by RefSeq, Jan 2016]

ACMG classification

Verdict is Benign. Variant got -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 = 0.691 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GLUD1	NM_005271.5	c.445+3928C>T		intron_variant		ENST00000277865.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLUD1	ENST00000277865.5	c.445+3928C>T		intron_variant		1	NM_005271.5	P1

Frequencies

GnomAD3 genomes AF: 0.283 AC: 42922 AN: 151888 Hom.: 6619 Cov.: 32

Gnomad AFR AF: 0.240

Gnomad AMI AF: 0.320

Gnomad AMR AF: 0.327

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.711

Gnomad SAS AF: 0.185

Gnomad FIN AF: 0.313

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.267

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

GnomAD4 genome AF: 0.283 AC: 42978 AN: 152000 Hom.: 6631 Cov.: 32 AF XY: 0.286 AC XY: 21257 AN XY: 74250

Gnomad4 AFR AF: 0.241

Gnomad4 AMR AF: 0.327

Gnomad4 ASJ AF: 0.227

Gnomad4 EAS AF: 0.711

Gnomad4 SAS AF: 0.186

Gnomad4 FIN AF: 0.313

Gnomad4 NFE AF: 0.272

Gnomad4 OTH AF: 0.269

Alfa AF: 0.273 Hom.: 723

Bravo AF: 0.288

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	7.5
Dann	Benign	0.66

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

Publications

LitVar

Other links and lift over

dbSNP: rs1923934; hg19: chr10-88850154;