rs2141709

Variant names:

• chr12-66145121-C-T
• rs2141709
• NM_016056.4:c.464+720G>A

Variant summary

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

The NM_016056.4(TMBIM4):​c.464+720G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.295 in 152,004 control chromosomes in the GnomAD database, including 7,177 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 0.30 (7177 hom., cov: 32)
• Consequence: TMBIM4 NM_016056.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.852
• Publications: 5 publications found

Genes affected

TMBIM4 (HGNC:24257): (transmembrane BAX inhibitor motif containing 4) Involved in negative regulation of apoptotic process and regulation of calcium-mediated signaling. Located in Golgi stack. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000228144 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.39 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016056.4. 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
	TMBIM4	NM_016056.4	MANE Select	c.464+720G>A		intron	N/A	NP_057140.2	Q9HC24
	TMBIM4	NM_001282606.2		c.605+720G>A		intron	N/A	NP_001269535.1	G3XAA5
	TMBIM4	NM_001282610.2		c.371+720G>A		intron	N/A	NP_001269539.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMBIM4	ENST00000358230.8	TSL:1 MANE Select	c.464+720G>A		intron	N/A	ENSP00000350965.3	Q9HC24
	TMBIM4	ENST00000542724.5	TSL:1	c.464+720G>A		intron	N/A	ENSP00000441291.2	G3V1M2
	TMBIM4	ENST00000398033.8	TSL:1	c.464+720G>A		intron	N/A	ENSP00000381114.4	E7EWY5

Frequencies

GnomAD3 genomes AF: 0.296 AC: 44898 AN: 151886 Hom.: 7183 Cov.: 32

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.216

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.379

Gnomad EAS AF: 0.335

Gnomad SAS AF: 0.405

Gnomad FIN AF: 0.357

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.354

Gnomad OTH AF: 0.262

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

GnomAD4 genome AF: 0.295 AC: 44894 AN: 152004 Hom.: 7177 Cov.: 32 AF XY: 0.298 AC XY: 22117 AN XY: 74296

African (AFR) AF: 0.179 AC: 7444 AN: 41474

American (AMR) AF: 0.246 AC: 3764 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.379 AC: 1315 AN: 3472

East Asian (EAS) AF: 0.334 AC: 1729 AN: 5170

South Asian (SAS) AF: 0.405 AC: 1953 AN: 4824

European-Finnish (FIN) AF: 0.357 AC: 3764 AN: 10532

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.354 AC: 24081 AN: 67934

Other (OTH) AF: 0.263 AC: 555 AN: 2108

Alfa AF: 0.306 Hom.: 960

Bravo AF: 0.278

Asia WGS AF: 0.340 AC: 1186 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	1.1
DANN	Benign	0.64
PhyloP100		-0.85
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: rs2141709; hg19: chr12-66538901;