8-97775979-C-T

Variant names:

• chr8-97775979-C-T
• rs757720337
• ENST00000445593.6:c.243C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The ENST00000445593.6(LAPTM4B):​c.243C>T​(p.Cys81Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000357 in 1,400,818 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000036 (0 hom.)
• Consequence: LAPTM4B ENST00000445593.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.101
• Publications: 1 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.045).
• BP7: Synonymous conserved (PhyloP=0.101 with no splicing effect.

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.-31C>T		5_prime_UTR	Exon 1 of 7	NP_060877.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAPTM4B	ENST00000445593.6	TSL:1	c.243C>T	p.Cys81Cys	synonymous	Exon 1 of 7	ENSP00000402301.2	Q86VI4-3
	LAPTM4B	ENST00000619747.1	TSL:1	c.243C>T	p.Cys81Cys	synonymous	Exon 1 of 7	ENSP00000482533.1	Q86VI4-3
	LAPTM4B	ENST00000521545.7	TSL:1 MANE Select	c.-31C>T		5_prime_UTR	Exon 1 of 7	ENSP00000428409.1	Q86VI4-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000234 AC: 4 AN: 170578 AF XY: 0.0000206

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000777

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000258

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000357 AC: 5 AN: 1400818 Hom.: 0 Cov.: 35 AF XY: 0.00000144 AC XY: 1 AN XY: 696098

African (AFR) AF: 0.00 AC: 0 AN: 29008

American (AMR) AF: 0.0000540 AC: 2 AN: 37032

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24518

East Asian (EAS) AF: 0.00 AC: 0 AN: 32516

South Asian (SAS) AF: 0.00 AC: 0 AN: 80274

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45178

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4914

European-Non Finnish (NFE) AF: 0.00000275 AC: 3 AN: 1089498

Other (OTH) AF: 0.00 AC: 0 AN: 57880

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	14
DANN	Benign	0.95
PhyloP100		0.10
PromoterAI		0.0028	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs757720337; hg19: chr8-98788207; COSMIC: COSV63392755; COSMIC: COSV63392755;