rs7785392

Variant names:

• chr7-100149755-G-T
• rs7785392
• NM_001008395.4:c.84+176G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
LAMTOR4	NM_001008395.4	c.84+176G>T		intron_variant	Intron 2 of 3	ENST00000341942.10	NP_001008396.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAMTOR4	ENST00000341942.10	c.84+176G>T		intron_variant	Intron 2 of 3	1	NM_001008395.4	ENSP00000343118.5

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

African (AFR) AF: 0.456 AC: 5215 AN: 11434

American (AMR) AF: 0.466 AC: 8034 AN: 17252

Ashkenazi Jewish (ASJ) AF: 0.606 AC: 6995 AN: 11534

East Asian (EAS) AF: 0.596 AC: 17300 AN: 29028

South Asian (SAS) AF: 0.586 AC: 19459 AN: 33212

European-Finnish (FIN) AF: 0.551 AC: 14888 AN: 27006

Middle Eastern (MID) AF: 0.617 AC: 1363 AN: 2208

European-Non Finnish (NFE) AF: 0.552 AC: 121235 AN: 219726

Other (OTH) AF: 0.541 AC: 11812 AN: 21846

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

African (AFR) AF: 0.461 AC: 19096 AN: 41458

American (AMR) AF: 0.465 AC: 7093 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.620 AC: 2152 AN: 3472

East Asian (EAS) AF: 0.642 AC: 3325 AN: 5182

South Asian (SAS) AF: 0.593 AC: 2862 AN: 4824

European-Finnish (FIN) AF: 0.573 AC: 6047 AN: 10556

Middle Eastern (MID) AF: 0.592 AC: 173 AN: 292

European-Non Finnish (NFE) AF: 0.553 AC: 37564 AN: 67984

Other (OTH) AF: 0.529 AC: 1120 AN: 2116

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
PhyloP100		2.2
PromoterAI		-0.0096	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7785392; hg19: chr7-99747378;