12-66151819-T-C

Position:

• chr12-66151819-T-C

Variant summary

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

The NM_016056.4(TMBIM4):​c.312+452A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.515 in 152,058 control chromosomes in the GnomAD database, including 21,622 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 0.52 (21622 hom., cov: 32)
• Consequence: TMBIM4 NM_016056.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.359

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]

ACMG classification

Verdict is Benign. Variant got -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 = 0.831 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMBIM4	NM_016056.4	c.312+452A>G		intron_variant		ENST00000358230.8	NP_057140.2
TMBIM4	NM_001282606.2	c.453+452A>G		intron_variant			NP_001269535.1
TMBIM4	NM_001282609.2	c.312+452A>G		intron_variant			NP_001269538.1
TMBIM4	NM_001282610.2	c.219+452A>G		intron_variant			NP_001269539.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMBIM4	ENST00000358230.8	c.312+452A>G		intron_variant		1	NM_016056.4	ENSP00000350965	P1

Frequencies

GnomAD3 genomes AF: 0.515 AC: 78238 AN: 151940 Hom.: 21586 Cov.: 32

Gnomad AFR AF: 0.670

Gnomad AMI AF: 0.377

Gnomad AMR AF: 0.356

Gnomad ASJ AF: 0.517

Gnomad EAS AF: 0.852

Gnomad SAS AF: 0.555

Gnomad FIN AF: 0.501

Gnomad MID AF: 0.458

Gnomad NFE AF: 0.434

Gnomad OTH AF: 0.454

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

GnomAD4 genome AF: 0.515 AC: 78324 AN: 152058 Hom.: 21622 Cov.: 32 AF XY: 0.519 AC XY: 38544 AN XY: 74330

Gnomad4 AFR AF: 0.671

Gnomad4 AMR AF: 0.356

Gnomad4 ASJ AF: 0.517

Gnomad4 EAS AF: 0.852

Gnomad4 SAS AF: 0.554

Gnomad4 FIN AF: 0.501

Gnomad4 NFE AF: 0.434

Gnomad4 OTH AF: 0.455

Alfa AF: 0.444 Hom.: 16983

Bravo AF: 0.510

Asia WGS AF: 0.665 AC: 2303 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.74
DANN	Benign	0.68

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: rs1168770; hg19: chr12-66545599;