rs2384687

chr19-55319820-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001282011.2(TMEM150B):c.324+219T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.383 in 1,374,612 control chromosomes in the GnomAD database, including 103,856 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 0.38 (11216 hom., cov: 31)
  • Exomes 𝑓: 0.38 (92640 hom.)
• Consequence: TMEM150B NM_001282011.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0910

Genes affected

TMEM150B (HGNC:34415): (transmembrane protein 150B) This gene encodes a protein that belongs to the DRAM (damage-regulated autophagy modulator) family of membrane-spanning proteins. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.448 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM150B	NM_001282011.2	c.324+219T>C		intron_variant		ENST00000326652.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM150B	ENST00000326652.9	c.324+219T>C		intron_variant		1	NM_001282011.2	P1

Frequencies

GnomAD3 genomes AF: 0.377 AC: 57188 AN: 151800 Hom.: 11194 Cov.: 31

Gnomad AFR AF: 0.400

Gnomad AMI AF: 0.319

Gnomad AMR AF: 0.385

Gnomad ASJ AF: 0.426

Gnomad EAS AF: 0.0817

Gnomad SAS AF: 0.463

Gnomad FIN AF: 0.321

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.384

Gnomad OTH AF: 0.382

GnomAD4 exome AF: 0.384 AC: 469458 AN: 1222692 Hom.: 92640 Cov.: 32 AF XY: 0.387 AC XY: 227769 AN XY: 589250

Gnomad4 AFR exome AF: 0.399

Gnomad4 AMR exome AF: 0.367

Gnomad4 ASJ exome AF: 0.414

Gnomad4 EAS exome AF: 0.0601

Gnomad4 SAS exome AF: 0.476

Gnomad4 FIN exome AF: 0.319

Gnomad4 NFE exome AF: 0.390

Gnomad4 OTH exome AF: 0.378

GnomAD4 genome AF: 0.377 AC: 57252 AN: 151920 Hom.: 11216 Cov.: 31 AF XY: 0.373 AC XY: 27714 AN XY: 74266

Gnomad4 AFR AF: 0.400

Gnomad4 AMR AF: 0.385

Gnomad4 ASJ AF: 0.426

Gnomad4 EAS AF: 0.0813

Gnomad4 SAS AF: 0.464

Gnomad4 FIN AF: 0.321

Gnomad4 NFE AF: 0.384

Gnomad4 OTH AF: 0.380

Alfa AF: 0.383 Hom.: 23285

Bravo AF: 0.382

Asia WGS AF: 0.305 AC: 1063 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	4.2
Dann	Benign	0.42

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

Publications

LitVar

Other links and lift over

dbSNP: rs2384687; hg19: chr19-55831188; COSMIC: COSV58595262;