chr1-151895052-C-T

Variant names:

• chr1-151895052-C-T
• rs114800758
• NM_053055.5:c.242G>A

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_053055.5(THEM4):​c.242G>A​(p.Arg81His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00931 in 1,613,964 control chromosomes in the GnomAD database, including 81 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0067 (6 hom., cov: 32)
  • Exomes 𝑓: 0.0096 (75 hom.)
• Consequence: THEM4 NM_053055.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.89
• Publications: 6 publications found

Genes affected

THEM4 (HGNC:17947): (thioesterase superfamily member 4) Protein kinase B (PKB) is a major downstream target of receptor tyrosine kinases that signal via phosphatidylinositol 3-kinase. Upon cell stimulation, PKB is translocated to the plasma membrane, where it is phosphorylated in the C-terminal regulatory domain. The protein encoded by this gene negatively regulates PKB activity by inhibiting phosphorylation. Transcription of this gene is commonly downregulated in glioblastomas. [provided by RefSeq, Jul 2008]

ENSG00000285651 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0033552647).
• BP6: Variant 1-151895052-C-T is Benign according to our data. Variant chr1-151895052-C-T is described in ClinVar as Benign. ClinVar VariationId is 770328.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 6 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_053055.5. 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
	THEM4	NM_053055.5	MANE Select	c.242G>A	p.Arg81His	missense	Exon 2 of 6	NP_444283.2	Q5T1C6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THEM4	ENST00000368814.8	TSL:1 MANE Select	c.242G>A	p.Arg81His	missense	Exon 2 of 6	ENSP00000357804.3	Q5T1C6
	THEM4	ENST00000471464.5	TSL:1	n.242G>A		non_coding_transcript_exon	Exon 2 of 7	ENSP00000431288.1	F6XC58
	THEM4	ENST00000489410.1	TSL:2	c.242G>A	p.Arg81His	missense	Exon 2 of 2	ENSP00000433304.1	E9PLJ7

Frequencies

GnomAD3 genomes AF: 0.00669 AC: 1017 AN: 152014 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.00157

Gnomad AMI AF: 0.00330

Gnomad AMR AF: 0.00151

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.0168

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0107

Gnomad OTH AF: 0.00526

GnomAD2 exomes AF: 0.00748 AC: 1881 AN: 251390 AF XY: 0.00735

Gnomad AFR exome AF: 0.00172

Gnomad AMR exome AF: 0.00130

Gnomad ASJ exome AF: 0.000298

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0177

Gnomad NFE exome AF: 0.0118

Gnomad OTH exome AF: 0.00554

GnomAD4 exome AF: 0.00959 AC: 14014 AN: 1461832 Hom.: 75 Cov.: 29 AF XY: 0.00924 AC XY: 6716 AN XY: 727212

African (AFR) AF: 0.00146 AC: 49 AN: 33478

American (AMR) AF: 0.00125 AC: 56 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.000574 AC: 15 AN: 26134

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39692

South Asian (SAS) AF: 0.00131 AC: 113 AN: 86258

European-Finnish (FIN) AF: 0.0164 AC: 878 AN: 53414

Middle Eastern (MID) AF: 0.000693 AC: 4 AN: 5768

European-Non Finnish (NFE) AF: 0.0112 AC: 12485 AN: 1111974

Other (OTH) AF: 0.00684 AC: 413 AN: 60392

GnomAD4 genome AF: 0.00668 AC: 1017 AN: 152132 Hom.: 6 Cov.: 32 AF XY: 0.00671 AC XY: 499 AN XY: 74384

African (AFR) AF: 0.00157 AC: 65 AN: 41482

American (AMR) AF: 0.00150 AC: 23 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4826

European-Finnish (FIN) AF: 0.0168 AC: 177 AN: 10564

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0107 AC: 727 AN: 68002

Other (OTH) AF: 0.00521 AC: 11 AN: 2112

Alfa AF: 0.00869 Hom.: 9

Bravo AF: 0.00510

TwinsUK AF: 0.0121 AC: 45

ALSPAC AF: 0.0119 AC: 46

ESP6500AA AF: 0.00318 AC: 14

ESP6500EA AF: 0.00953 AC: 82

ExAC AF: 0.00798 AC: 969

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00900

EpiControl AF: 0.00741

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.0080
DANN	Benign	0.73
DEOGEN2	Benign	0.36	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0032	N
LIST_S2	Benign	0.35	T
MetaRNN	Benign	0.0034	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
PhyloP100		-3.9
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.021
Sift	Benign	0.47	T
Sift4G	Benign	0.37	T
Polyphen		0.35	B
Vest4		0.069
MVP		0.014
MPC		0.098
ClinPred		0.0070	T
GERP RS		-6.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.057
gMVP		0.35
Mutation Taster		=98/2	polymorphism

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: rs114800758; hg19: chr1-151867528; COSMIC: COSV64295580; COSMIC: COSV64295580;