6-158170266-A-C

Position:

• chr6-158170266-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_207118.3(GTF2H5):​c.-34-204A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0228 in 152,234 control chromosomes in the GnomAD database, including 51 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.023 (51 hom., cov: 32)
• Consequence: GTF2H5 NM_207118.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0210

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=-0.86).
• BP6: Variant 6-158170266-A-C is Benign according to our data. Variant chr6-158170266-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 1187034.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0228 (3472/152234) while in subpopulation NFE AF= 0.0354 (2405/68024). AF 95% confidence interval is 0.0342. There are 51 homozygotes in gnomad4. There are 1602 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 51 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GTF2H5	NM_207118.3	c.-34-204A>C		intron_variant		ENST00000607778.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GTF2H5	ENST00000607778.2	c.-34-204A>C		intron_variant		1	NM_207118.3	P1

Frequencies

GnomAD3 genomes AF: 0.0229 AC: 3478 AN: 152116 Hom.: 51 Cov.: 32

Gnomad AFR AF: 0.00729

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.0196

Gnomad ASJ AF: 0.0455

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0235

Gnomad FIN AF: 0.00622

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0354

Gnomad OTH AF: 0.0296

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

GnomAD4 genome AF: 0.0228 AC: 3472 AN: 152234 Hom.: 51 Cov.: 32 AF XY: 0.0215 AC XY: 1602 AN XY: 74442

Gnomad4 AFR AF: 0.00727

Gnomad4 AMR AF: 0.0196

Gnomad4 ASJ AF: 0.0455

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0235

Gnomad4 FIN AF: 0.00622

Gnomad4 NFE AF: 0.0354

Gnomad4 OTH AF: 0.0293

Alfa AF: 0.0256 Hom.: 4

Bravo AF: 0.0237

Asia WGS AF: 0.0120 AC: 43 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.96
DANN	Benign	0.65

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: rs118000494; hg19: chr6-158591298;