rs4560672

Positions:

• chr6-158186441-C-A
• chr6-158186441-C-T

Variant summary

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

The NM_207118.3(GTF2H5):​c.36-5536C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 152,212 control chromosomes in the GnomAD database, including 6,016 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 0.22 (6016 hom., cov: 33)
• Consequence: GTF2H5 NM_207118.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.31

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]

GTF2H5 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.487 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GTF2H5	NM_207118.3	c.36-5536C>A		intron_variant		ENST00000607778.2	NP_997001.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GTF2H5	ENST00000607778.2	c.36-5536C>A		intron_variant		1	NM_207118.3	ENSP00000476100.1

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33889 AN: 152094 Hom.: 6003 Cov.: 33

Gnomad AFR AF: 0.493

Gnomad AMI AF: 0.0658

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.142

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.0882

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.136

Gnomad OTH AF: 0.181

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

GnomAD4 genome AF: 0.223 AC: 33940 AN: 152212 Hom.: 6016 Cov.: 33 AF XY: 0.217 AC XY: 16146 AN XY: 74430

Gnomad4 AFR AF: 0.493

Gnomad4 AMR AF: 0.116

Gnomad4 ASJ AF: 0.142

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.115

Gnomad4 FIN AF: 0.0882

Gnomad4 NFE AF: 0.136

Gnomad4 OTH AF: 0.181

Alfa AF: 0.182 Hom.: 873

Bravo AF: 0.235

Asia WGS AF: 0.0810 AC: 285 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.033
DANN	Benign	0.20

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: rs4560672; hg19: chr6-158607473; COSMIC: COSV74156315;