chr8-97835027-T-C

Variant names:

• chr8-97835027-T-C
• rs2449539
• NM_018407.6:c.603+9874T>C

Variant summary

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

The NM_018407.6(LAPTM4B):​c.603+9874T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0763 in 152,278 control chromosomes in the GnomAD database, including 998 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 0.076 (998 hom., cov: 33)
• Consequence: LAPTM4B NM_018407.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.23
• Publications: 3 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.353 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018407.6. 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.603+9874T>C		intron	N/A	NP_060877.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAPTM4B	ENST00000521545.7	TSL:1 MANE Select	c.603+9874T>C		intron	N/A	ENSP00000428409.1	Q86VI4-2
	LAPTM4B	ENST00000445593.6	TSL:1	c.876+9874T>C		intron	N/A	ENSP00000402301.2	Q86VI4-3
	LAPTM4B	ENST00000619747.1	TSL:1	c.876+9874T>C		intron	N/A	ENSP00000482533.1	Q86VI4-3

Frequencies

GnomAD3 genomes AF: 0.0762 AC: 11599 AN: 152160 Hom.: 993 Cov.: 33

Gnomad AFR AF: 0.0645

Gnomad AMI AF: 0.0264

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.0528

Gnomad EAS AF: 0.365

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.0847

Gnomad MID AF: 0.0860

Gnomad NFE AF: 0.0270

Gnomad OTH AF: 0.0941

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

GnomAD4 genome AF: 0.0763 AC: 11618 AN: 152278 Hom.: 998 Cov.: 33 AF XY: 0.0855 AC XY: 6366 AN XY: 74468

African (AFR) AF: 0.0645 AC: 2683 AN: 41566

American (AMR) AF: 0.183 AC: 2804 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0528 AC: 183 AN: 3468

East Asian (EAS) AF: 0.366 AC: 1894 AN: 5170

South Asian (SAS) AF: 0.221 AC: 1063 AN: 4812

European-Finnish (FIN) AF: 0.0847 AC: 898 AN: 10600

Middle Eastern (MID) AF: 0.0856 AC: 25 AN: 292

European-Non Finnish (NFE) AF: 0.0270 AC: 1840 AN: 68042

Other (OTH) AF: 0.0964 AC: 204 AN: 2116

Alfa AF: 0.0485 Hom.: 558

Bravo AF: 0.0829

Asia WGS AF: 0.271 AC: 938 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.23
DANN	Benign	0.61
PhyloP100		-2.2
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: rs2449539; hg19: chr8-98847255;