chr6-158170256-C-G

Position:

• chr6-158170256-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_207118.3(GTF2H5):​c.-34-214C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 152,040 control chromosomes in the GnomAD database, including 1,303 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.12 (1303 hom., cov: 31)
• Consequence: GTF2H5 NM_207118.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.376

Genes affected

GTF2H5 (HGNC:21157): (general transcription factor IIH subunit 5) This gene encodes a subunit of transcription/repair factor TFIIH, which functions in gene transcription and DNA repair. This protein stimulates ERCC3/XPB ATPase activity to trigger DNA opening during DNA repair, and is implicated in regulating cellular levels of TFIIH. Mutations in this gene result in trichothiodystrophy, complementation group A. [provided by RefSeq, Mar 2009]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 6-158170256-C-G is Benign according to our data. Variant chr6-158170256-C-G is described in ClinVar as [Benign]. Clinvar id is 1288642.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GTF2H5	NM_207118.3	c.-34-214C>G		intron_variant		ENST00000607778.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GTF2H5	ENST00000607778.2	c.-34-214C>G		intron_variant		1	NM_207118.3	P1

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18843 AN: 151922 Hom.: 1299 Cov.: 31

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.0658

Gnomad AMR AF: 0.0799

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.0881

Gnomad MID AF: 0.162

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.105

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

GnomAD4 genome AF: 0.124 AC: 18862 AN: 152040 Hom.: 1303 Cov.: 31 AF XY: 0.121 AC XY: 9018 AN XY: 74342

Gnomad4 AFR AF: 0.151

Gnomad4 AMR AF: 0.0798

Gnomad4 ASJ AF: 0.118

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.114

Gnomad4 FIN AF: 0.0881

Gnomad4 NFE AF: 0.135

Gnomad4 OTH AF: 0.105

Alfa AF: 0.133 Hom.: 151

Bravo AF: 0.123

Asia WGS AF: 0.0640 AC: 222 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.9
DANN	Benign	0.23

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: rs78146749; hg19: chr6-158591288;