rs7785392

chr7-100149755-G-T

Variant summary

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

The NM_001008395.4(LAMTOR4):c.84+176G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.545 in 525,304 control chromosomes in the GnomAD database, including 78,961 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 0.53 (21332 hom., cov: 32)
  • Exomes 𝑓: 0.55 (57629 hom.)
• Consequence: LAMTOR4 NM_001008395.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.21

Genes affected

LAMTOR4 (HGNC:33772): (late endosomal/lysosomal adaptor, MAPK and MTOR activator 4) Contributes to guanyl-nucleotide exchange factor activity and molecular adaptor activity. Involved in several processes, including cellular response to amino acid stimulus; positive regulation of TOR signaling; and protein localization to lysosome. Located in lysosome. Part of Ragulator complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.623 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LAMTOR4	NM_001008395.4	c.84+176G>T		intron_variant		ENST00000341942.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LAMTOR4	ENST00000341942.10	c.84+176G>T		intron_variant		1	NM_001008395.4	P1

Frequencies

GnomAD3 genomes AF: 0.526 AC: 79967 AN: 151940 Hom.: 21315 Cov.: 32

Gnomad AFR AF: 0.461

Gnomad AMI AF: 0.652

Gnomad AMR AF: 0.464

Gnomad ASJ AF: 0.620

Gnomad EAS AF: 0.641

Gnomad SAS AF: 0.592

Gnomad FIN AF: 0.573

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.553

Gnomad OTH AF: 0.530

GnomAD4 exome AF: 0.553 AC: 206301 AN: 373246 Hom.: 57629 Cov.: 4 AF XY: 0.557 AC XY: 109227 AN XY: 196154

Gnomad4 AFR exome AF: 0.456

Gnomad4 AMR exome AF: 0.466

Gnomad4 ASJ exome AF: 0.606

Gnomad4 EAS exome AF: 0.596

Gnomad4 SAS exome AF: 0.586

Gnomad4 FIN exome AF: 0.551

Gnomad4 NFE exome AF: 0.552

Gnomad4 OTH exome AF: 0.541

GnomAD4 genome AF: 0.526 AC: 80027 AN: 152058 Hom.: 21332 Cov.: 32 AF XY: 0.529 AC XY: 39338 AN XY: 74316

Gnomad4 AFR AF: 0.461

Gnomad4 AMR AF: 0.465

Gnomad4 ASJ AF: 0.620

Gnomad4 EAS AF: 0.642

Gnomad4 SAS AF: 0.593

Gnomad4 FIN AF: 0.573

Gnomad4 NFE AF: 0.553

Gnomad4 OTH AF: 0.529

Alfa AF: 0.519 Hom.: 3949

Bravo AF: 0.518

Asia WGS AF: 0.614 AC: 2137 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	8.6
Dann	Benign	0.73

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

Publications

LitVar

Other links and lift over

dbSNP: rs7785392; hg19: chr7-99747378;