12-66167099-G-A

Variant names:

• chr12-66167099-G-A
• rs1185888
• NM_016056.4:c.97+2756C>T

Variant summary

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

The NM_016056.4(TMBIM4):​c.97+2756C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.504 in 152,086 control chromosomes in the GnomAD database, including 20,638 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 0.50 (20638 hom., cov: 33)
• Consequence: TMBIM4 NM_016056.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.55
• Publications: 13 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.771 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMBIM4	NM_016056.4	c.97+2756C>T		intron_variant	Intron 1 of 6	ENST00000358230.8	NP_057140.2
TMBIM4	NM_001282606.2	c.97+2756C>T		intron_variant	Intron 1 of 7		NP_001269535.1
TMBIM4	NM_001282610.2	c.42+2756C>T		intron_variant	Intron 1 of 6		NP_001269539.1
TMBIM4	NM_001282609.2	c.97+2756C>T		intron_variant	Intron 1 of 6		NP_001269538.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMBIM4	ENST00000358230.8	c.97+2756C>T		intron_variant	Intron 1 of 6	1	NM_016056.4	ENSP00000350965.3
ENSG00000228144	ENST00000539652.1	n.97+2756C>T		intron_variant	Intron 1 of 7	2		ENSP00000454670.1

Frequencies

GnomAD3 genomes AF: 0.504 AC: 76620 AN: 151968 Hom.: 20616 Cov.: 33

Gnomad AFR AF: 0.664

Gnomad AMI AF: 0.367

Gnomad AMR AF: 0.363

Gnomad ASJ AF: 0.475

Gnomad EAS AF: 0.791

Gnomad SAS AF: 0.555

Gnomad FIN AF: 0.471

Gnomad MID AF: 0.442

Gnomad NFE AF: 0.424

Gnomad OTH AF: 0.442

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

GnomAD4 genome AF: 0.504 AC: 76686 AN: 152086 Hom.: 20638 Cov.: 33 AF XY: 0.507 AC XY: 37727 AN XY: 74346

African (AFR) AF: 0.664 AC: 27542 AN: 41504

American (AMR) AF: 0.362 AC: 5538 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.475 AC: 1648 AN: 3466

East Asian (EAS) AF: 0.791 AC: 4094 AN: 5176

South Asian (SAS) AF: 0.554 AC: 2673 AN: 4822

European-Finnish (FIN) AF: 0.471 AC: 4977 AN: 10556

Middle Eastern (MID) AF: 0.445 AC: 129 AN: 290

European-Non Finnish (NFE) AF: 0.424 AC: 28814 AN: 67968

Other (OTH) AF: 0.443 AC: 936 AN: 2112

Alfa AF: 0.452 Hom.: 2599

Bravo AF: 0.503

Asia WGS AF: 0.636 AC: 2212 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.44
DANN	Benign	0.48
PhyloP100		-2.5
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: rs1185888; hg19: chr12-66560879;