8-30641342-T-C

Position:

• chr8-30641342-T-C

Variant summary

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

The NM_002095.6(GTF2E2):​c.167-6219A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.8 in 152,096 control chromosomes in the GnomAD database, including 49,149 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 0.80 (49149 hom., cov: 30)
• Consequence: GTF2E2 NM_002095.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00300

Genes affected

SMIM18 (HGNC:42973): (small integral membrane protein 18) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

GTF2E2 (HGNC:4651): (general transcription factor IIE subunit 2) The general transcription factor IIE (TFIIE) is part of the RNA polymerase II transcription initiation complex, recruiting TFIIH and being essential for promoter clearance by RNA polymerase II. TFIIE is a heterodimer (and sometimes heterotetramer) of alpha and beta subunits. The protein encoded by this gene represents the beta subunit of TFIIE. [provided by RefSeq, Jan 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.882 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMIM18	NM_001206847.2	c.-111+2703T>C		intron_variant		ENST00000517349.2	NP_001193776.1
GTF2E2	NM_002095.6	c.167-6219A>G		intron_variant		ENST00000355904.9	NP_002086.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GTF2E2	ENST00000355904.9	c.167-6219A>G		intron_variant		1	NM_002095.6	ENSP00000348168	P1
SMIM18	ENST00000517349.2	c.-111+2703T>C		intron_variant		2	NM_001206847.2	ENSP00000428858	P1

Frequencies

GnomAD3 genomes AF: 0.800 AC: 121529 AN: 151978 Hom.: 49108 Cov.: 30

Gnomad AFR AF: 0.890

Gnomad AMI AF: 0.856

Gnomad AMR AF: 0.668

Gnomad ASJ AF: 0.861

Gnomad EAS AF: 0.572

Gnomad SAS AF: 0.784

Gnomad FIN AF: 0.825

Gnomad MID AF: 0.810

Gnomad NFE AF: 0.785

Gnomad OTH AF: 0.787

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

GnomAD4 genome AF: 0.800 AC: 121619 AN: 152096 Hom.: 49149 Cov.: 30 AF XY: 0.797 AC XY: 59229 AN XY: 74324

Gnomad4 AFR AF: 0.890

Gnomad4 AMR AF: 0.668

Gnomad4 ASJ AF: 0.861

Gnomad4 EAS AF: 0.572

Gnomad4 SAS AF: 0.784

Gnomad4 FIN AF: 0.825

Gnomad4 NFE AF: 0.785

Gnomad4 OTH AF: 0.785

Alfa AF: 0.781 Hom.: 96238

Bravo AF: 0.788

Asia WGS AF: 0.677 AC: 2353 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	6.5
DANN	Benign	0.45

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: rs2978263; hg19: chr8-30498859;