chr8-97805403-G-A

Variant names:

• chr8-97805403-G-A
• rs115788337
• NM_018407.6:c.150G>A

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_018407.6(LAPTM4B):​c.150G>A​(p.Pro50Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000311 in 1,609,960 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0015 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00019 (6 hom.)
• Consequence: LAPTM4B NM_018407.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.98
• 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]

ACMG classification

Our verdict: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.026).
• BP6: Variant 8-97805403-G-A is Benign according to our data. Variant chr8-97805403-G-A is described in ClinVar as [Benign]. Clinvar id is 732085.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.98 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAPTM4B	NM_018407.6	c.150G>A	p.Pro50Pro	synonymous_variant	Exon 2 of 7	ENST00000521545.7	NP_060877.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAPTM4B	ENST00000521545.7	c.150G>A	p.Pro50Pro	synonymous_variant	Exon 2 of 7	1	NM_018407.6	ENSP00000428409.1
LAPTM4B	ENST00000445593.6	c.423G>A	p.Pro141Pro	synonymous_variant	Exon 2 of 7	1		ENSP00000402301.2
LAPTM4B	ENST00000619747.1	c.423G>A	p.Pro141Pro	synonymous_variant	Exon 2 of 7	1		ENSP00000482533.1
LAPTM4B	ENST00000517924.5	c.150G>A	p.Pro50Pro	synonymous_variant	Exon 2 of 5	5		ENSP00000429868.2

Frequencies

GnomAD3 genomes AF: 0.00150 AC: 223 AN: 149126 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00421

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00313

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000210

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000738

Gnomad OTH AF: 0.000990

GnomAD2 exomes AF: 0.000370 AC: 93 AN: 251318 AF XY: 0.000346

Gnomad AFR exome AF: 0.00418

Gnomad AMR exome AF: 0.000318

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000792

Gnomad OTH exome AF: 0.000815

GnomAD4 exome AF: 0.000190 AC: 277 AN: 1460740 Hom.: 6 Cov.: 31 AF XY: 0.000189 AC XY: 137 AN XY: 726698

African (AFR) AF: 0.00469 AC: 157 AN: 33442

American (AMR) AF: 0.000425 AC: 19 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26106

East Asian (EAS) AF: 0.00 AC: 0 AN: 39672

South Asian (SAS) AF: 0.0000580 AC: 5 AN: 86232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53342

Middle Eastern (MID) AF: 0.00313 AC: 18 AN: 5754

European-Non Finnish (NFE) AF: 0.0000405 AC: 45 AN: 1111162

Other (OTH) AF: 0.000547 AC: 33 AN: 60336

GnomAD4 genome AF: 0.00150 AC: 224 AN: 149220 Hom.: 0 Cov.: 31 AF XY: 0.00135 AC XY: 98 AN XY: 72558

African (AFR) AF: 0.00422 AC: 170 AN: 40272

American (AMR) AF: 0.00313 AC: 46 AN: 14706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3458

East Asian (EAS) AF: 0.00 AC: 0 AN: 5098

South Asian (SAS) AF: 0.000211 AC: 1 AN: 4740

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9996

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 280

European-Non Finnish (NFE) AF: 0.0000738 AC: 5 AN: 67722

Other (OTH) AF: 0.000982 AC: 2 AN: 2036

Alfa AF: 0.000722 Hom.: 0

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 02, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.26
DANN	Benign	0.36
PhyloP100		-2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs115788337; hg19: chr8-98817631;