rs925530

Positions:

• chr12-121725370-G-A

Variant summary

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

The NM_001080825.2(TMEM120B):​c.69+12406G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 151,936 control chromosomes in the GnomAD database, including 13,313 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 0.41 (13313 hom., cov: 32)
• Consequence: TMEM120B NM_001080825.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.05

Genes affected

TMEM120B (HGNC:32008): (transmembrane protein 120B) Predicted to be involved in fat cell differentiation and protein heterooligomerization. Predicted to be integral component of membrane. Predicted to be active in nuclear inner membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.538 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM120B	NM_001080825.2	c.69+12406G>A		intron_variant		ENST00000449592.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM120B	ENST00000449592.7	c.69+12406G>A		intron_variant		1	NM_001080825.2	P1
TMEM120B	ENST00000342607.10	c.69+12406G>A		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.410 AC: 62171 AN: 151816 Hom.: 13291 Cov.: 32

Gnomad AFR AF: 0.545

Gnomad AMI AF: 0.348

Gnomad AMR AF: 0.388

Gnomad ASJ AF: 0.308

Gnomad EAS AF: 0.425

Gnomad SAS AF: 0.381

Gnomad FIN AF: 0.375

Gnomad MID AF: 0.274

Gnomad NFE AF: 0.346

Gnomad OTH AF: 0.366

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

GnomAD4 genome AF: 0.410 AC: 62244 AN: 151936 Hom.: 13313 Cov.: 32 AF XY: 0.407 AC XY: 30233 AN XY: 74276

Gnomad4 AFR AF: 0.544

Gnomad4 AMR AF: 0.389

Gnomad4 ASJ AF: 0.308

Gnomad4 EAS AF: 0.425

Gnomad4 SAS AF: 0.382

Gnomad4 FIN AF: 0.375

Gnomad4 NFE AF: 0.346

Gnomad4 OTH AF: 0.368

Alfa AF: 0.365 Hom.: 9918

Bravo AF: 0.419

Asia WGS AF: 0.412 AC: 1435 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.011
DANN	Benign	0.37

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: rs925530; hg19: chr12-122163276;