12-66137019-C-G

Variant names:

• chr12-66137019-C-G
• rs1168754
• NM_016056.4:c.*941G>C

Variant summary

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

The NM_016056.4(TMBIM4):​c.*941G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.781 in 152,200 control chromosomes in the GnomAD database, including 47,450 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 0.78 (47450 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: TMBIM4 NM_016056.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.794
• 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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.93 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.*941G>C		3_prime_UTR	Exon 7 of 7	NP_057140.2	Q9HC24
	TMBIM4	NM_001282606.2		c.*941G>C		3_prime_UTR	Exon 8 of 8	NP_001269535.1	G3XAA5
	TMBIM4	NM_001282610.2		c.*941G>C		3_prime_UTR	Exon 7 of 7	NP_001269539.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMBIM4	ENST00000358230.8	TSL:1 MANE Select	c.*941G>C		3_prime_UTR	Exon 7 of 7	ENSP00000350965.3	Q9HC24
	TMBIM4	ENST00000544599.5	TSL:1	c.*941G>C		3_prime_UTR	Exon 7 of 7	ENSP00000444639.1	G3V1R8
	ENSG00000228144	ENST00000539652.1	TSL:2	n.*123+945G>C		intron	N/A	ENSP00000454670.1	F6UZH7

Frequencies

GnomAD3 genomes AF: 0.781 AC: 118776 AN: 152082 Hom.: 47400 Cov.: 33

Gnomad AFR AF: 0.938

Gnomad AMI AF: 0.811

Gnomad AMR AF: 0.621

Gnomad ASJ AF: 0.813

Gnomad EAS AF: 0.880

Gnomad SAS AF: 0.756

Gnomad FIN AF: 0.710

Gnomad MID AF: 0.778

Gnomad NFE AF: 0.725

Gnomad OTH AF: 0.752

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.781 AC: 118882 AN: 152200 Hom.: 47450 Cov.: 33 AF XY: 0.779 AC XY: 57981 AN XY: 74394

African (AFR) AF: 0.938 AC: 38970 AN: 41548

American (AMR) AF: 0.621 AC: 9495 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.813 AC: 2823 AN: 3472

East Asian (EAS) AF: 0.880 AC: 4568 AN: 5188

South Asian (SAS) AF: 0.756 AC: 3641 AN: 4814

European-Finnish (FIN) AF: 0.710 AC: 7501 AN: 10570

Middle Eastern (MID) AF: 0.786 AC: 231 AN: 294

European-Non Finnish (NFE) AF: 0.725 AC: 49332 AN: 68004

Other (OTH) AF: 0.749 AC: 1581 AN: 2112

Alfa AF: 0.732 Hom.: 4884

Bravo AF: 0.778

Asia WGS AF: 0.807 AC: 2805 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.6
DANN	Benign	0.59
PhyloP100		-0.79
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: rs1168754; hg19: chr12-66530799;