8-97775784-C-T

Variant names:

• chr8-97775784-C-T
• rs114241480
• ENST00000445593.6:c.48C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The ENST00000445593.6(LAPTM4B):​c.48C>T​(p.Leu16Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00307 in 1,552,084 control chromosomes in the GnomAD database, including 145 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.017 (79 hom., cov: 31)
  • Exomes 𝑓: 0.0016 (66 hom.)
• Consequence: LAPTM4B ENST00000445593.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.281
• Publications: 0 publications found

Genes affected

LAPTM4B (HGNC:13646): (lysosomal protein transmembrane 4 beta) Enables ceramide binding activity; enzyme binding activity; and phosphatidylinositol bisphosphate binding activity. Involved in several processes, including negative regulation of macromolecule metabolic process; regulation of lysosomal membrane permeability; and regulation of lysosome organization. Located in several cellular components, including endosome; lysosomal membrane; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

LOC124901986 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 8-97775784-C-T is Benign according to our data. Variant chr8-97775784-C-T is described in ClinVar as Benign. ClinVar VariationId is 775266.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.281 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0538 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000445593.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAPTM4B	NM_018407.6	MANE Select	c.-226C>T		upstream_gene	N/A	NP_060877.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAPTM4B	ENST00000445593.6	TSL:1	c.48C>T	p.Leu16Leu	synonymous	Exon 1 of 7	ENSP00000402301.2	Q86VI4-3
	LAPTM4B	ENST00000619747.1	TSL:1	c.48C>T	p.Leu16Leu	synonymous	Exon 1 of 7	ENSP00000482533.1	Q86VI4-3
	LAPTM4B	ENST00000929553.1		c.-226C>T		5_prime_UTR	Exon 1 of 6	ENSP00000599612.1

Frequencies

GnomAD3 genomes AF: 0.0166 AC: 2458 AN: 147672 Hom.: 79 Cov.: 31

Gnomad AFR AF: 0.0557

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00801

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000170

Gnomad OTH AF: 0.0161

GnomAD2 exomes AF: 0.00372 AC: 645 AN: 173534 AF XY: 0.00268

Gnomad AFR exome AF: 0.0579

Gnomad AMR exome AF: 0.00312

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000818

Gnomad OTH exome AF: 0.00170

GnomAD4 exome AF: 0.00164 AC: 2309 AN: 1404302 Hom.: 66 Cov.: 40 AF XY: 0.00143 AC XY: 996 AN XY: 696540

African (AFR) AF: 0.0574 AC: 1863 AN: 32464

American (AMR) AF: 0.00333 AC: 134 AN: 40256

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25272

East Asian (EAS) AF: 0.00 AC: 0 AN: 37568

South Asian (SAS) AF: 0.000108 AC: 9 AN: 83324

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35924

Middle Eastern (MID) AF: 0.00316 AC: 15 AN: 4748

European-Non Finnish (NFE) AF: 0.0000709 AC: 77 AN: 1086368

Other (OTH) AF: 0.00361 AC: 211 AN: 58378

GnomAD4 genome AF: 0.0167 AC: 2462 AN: 147782 Hom.: 79 Cov.: 31 AF XY: 0.0165 AC XY: 1197 AN XY: 72406

African (AFR) AF: 0.0557 AC: 2295 AN: 41232

American (AMR) AF: 0.00800 AC: 119 AN: 14878

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3392

East Asian (EAS) AF: 0.00 AC: 0 AN: 5118

South Asian (SAS) AF: 0.00 AC: 0 AN: 4738

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10386

Middle Eastern (MID) AF: 0.0137 AC: 4 AN: 292

European-Non Finnish (NFE) AF: 0.000170 AC: 11 AN: 64768

Other (OTH) AF: 0.0160 AC: 33 AN: 2066

Alfa AF: 0.000968 Hom.: 0

Bravo AF: 0.0185

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	3.5
DANN	Benign	0.94
PhyloP100		0.28
PromoterAI		0.22	Neutral
Mutation Taster		=300/0	polymorphism

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: rs114241480; hg19: chr8-98788012;