22-24590505-T-C

Variant names:

• chr22-24590505-T-C
• rs5760485
• NM_207644.3:c.178-556A>G

Variant summary

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

The NM_207644.3(LRRC75B):​c.178-556A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.407 in 151,882 control chromosomes in the GnomAD database, including 15,106 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 0.41 (15106 hom., cov: 31)
• Consequence: LRRC75B NM_207644.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.120
• Publications: 9 publications found

Genes affected

LRRC75B (HGNC:33155): (leucine rich repeat containing 75B) Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000286070 (HGNC:):

GGT1 (HGNC:4250): (gamma-glutamyltransferase 1) The enzyme encoded by this gene is a type I gamma-glutamyltransferase that catalyzes the transfer of the glutamyl moiety of glutathione to a variety of amino acids and dipeptide acceptors. The enzyme is composed of a heavy chain and a light chain, which are derived from a single precursor protein. It is expressed in tissues involved in absorption and secretion and may contribute to the etiology of diabetes and other metabolic disorders. Multiple alternatively spliced variants have been identified. There are a number of related genes present on chromosomes 20 and 22, and putative pseudogenes for this gene on chromosomes 2, 13, and 22. [provided by RefSeq, Jan 2014]

GGT1 Gene-Disease associations (from GenCC):

• gamma-glutamyl transpeptidase deficiency

  Inheritance: AR Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.681 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC75B	NM_207644.3	c.178-556A>G		intron_variant	Intron 1 of 3	ENST00000318753.13	NP_997527.2
GGT1	NM_013430.3	c.-429+6697T>C		intron_variant	Intron 1 of 15		NP_038347.2
LRRC75B	XM_047441360.1	c.178-556A>G		intron_variant	Intron 1 of 2		XP_047297316.1
LRRC75B	XM_005261600.4	c.178-556A>G		intron_variant	Intron 1 of 3		XP_005261657.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRC75B	ENST00000318753.13	c.178-556A>G		intron_variant	Intron 1 of 3	1	NM_207644.3	ENSP00000320520.8
ENSG00000286070	ENST00000652248.1	n.*167+6697T>C		intron_variant	Intron 5 of 19			ENSP00000499210.1

Frequencies

GnomAD3 genomes AF: 0.407 AC: 61769 AN: 151766 Hom.: 15087 Cov.: 31

Gnomad AFR AF: 0.689

Gnomad AMI AF: 0.175

Gnomad AMR AF: 0.429

Gnomad ASJ AF: 0.319

Gnomad EAS AF: 0.231

Gnomad SAS AF: 0.258

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.420

Gnomad NFE AF: 0.290

Gnomad OTH AF: 0.401

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

GnomAD4 genome AF: 0.407 AC: 61840 AN: 151882 Hom.: 15106 Cov.: 31 AF XY: 0.399 AC XY: 29653 AN XY: 74226

African (AFR) AF: 0.688 AC: 28491 AN: 41400

American (AMR) AF: 0.429 AC: 6550 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.319 AC: 1107 AN: 3466

East Asian (EAS) AF: 0.232 AC: 1188 AN: 5130

South Asian (SAS) AF: 0.259 AC: 1244 AN: 4810

European-Finnish (FIN) AF: 0.233 AC: 2461 AN: 10572

Middle Eastern (MID) AF: 0.428 AC: 125 AN: 292

European-Non Finnish (NFE) AF: 0.290 AC: 19680 AN: 67926

Other (OTH) AF: 0.396 AC: 834 AN: 2106

Alfa AF: 0.335 Hom.: 13610

Bravo AF: 0.438

Asia WGS AF: 0.253 AC: 879 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.1
DANN	Benign	0.39
PhyloP100		0.12
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: rs5760485; hg19: chr22-24986473;