rs2384687

Variant names:

• chr19-55319820-A-G
• rs2384687
• NM_001282011.2:c.324+219T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 16 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001282011.2. 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
	TMEM150B	NM_001282011.2	MANE Select	c.324+219T>C		intron	N/A	NP_001268940.1	A6NC51
	TMEM150B	NM_001085488.3		c.324+219T>C		intron	N/A	NP_001078957.1	A6NC51
	TMEM150B	NR_104066.2		n.479+219T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM150B	ENST00000326652.9	TSL:1 MANE Select	c.324+219T>C		intron	N/A	ENSP00000320757.4	A6NC51
	TMEM150B	ENST00000592891.1	TSL:1	n.841T>C		non_coding_transcript_exon	Exon 6 of 6
	TMEM150B	ENST00000586609.5	TSL:1	n.*64+219T>C		intron	N/A	ENSP00000466957.1	K7ENI3

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

African (AFR) AF: 0.399 AC: 10694 AN: 26834

American (AMR) AF: 0.367 AC: 5616 AN: 15320

Ashkenazi Jewish (ASJ) AF: 0.414 AC: 7138 AN: 17238

East Asian (EAS) AF: 0.0601 AC: 1844 AN: 30696

South Asian (SAS) AF: 0.476 AC: 26067 AN: 54718

European-Finnish (FIN) AF: 0.319 AC: 8619 AN: 26984

Middle Eastern (MID) AF: 0.338 AC: 1113 AN: 3292

European-Non Finnish (NFE) AF: 0.390 AC: 389451 AN: 997610

Other (OTH) AF: 0.378 AC: 18916 AN: 50000

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

African (AFR) AF: 0.400 AC: 16565 AN: 41440

American (AMR) AF: 0.385 AC: 5864 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.426 AC: 1476 AN: 3464

East Asian (EAS) AF: 0.0813 AC: 419 AN: 5152

South Asian (SAS) AF: 0.464 AC: 2220 AN: 4786

European-Finnish (FIN) AF: 0.321 AC: 3398 AN: 10586

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.384 AC: 26129 AN: 67974

Other (OTH) AF: 0.380 AC: 798 AN: 2102

Alfa AF: 0.383 Hom.: 35456

Bravo AF: 0.382

Asia WGS AF: 0.305 AC: 1063 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.2
DANN	Benign	0.42
PhyloP100		-0.091
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: rs2384687; hg19: chr19-55831188; COSMIC: COSV58595262;