Genetic Variant NM_001517.5:c.560+51C>A (chr6-30910992-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001517.5(GTF2H4):c.560+51C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

GTF2H4
NM_001517.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0580

Publications

17 publications found

Variant links:

Genes affected

GTF2H4 (HGNC:4658): (general transcription factor IIH subunit 4) Enables RNA polymerase II general transcription initiation factor activity. Involved in transcription by RNA polymerase II. Located in nuclear speck. Part of core TFIIH complex portion of holo TFIIH complex and transcription factor TFIID complex. [provided by Alliance of Genome Resources, Apr 2022]

GTF2H4 links:

ENSG00000288473 (HGNC:):

ENSG00000288473 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GTF2H4	NM_001517.5 link	c.560+51C>A		intron_variant	Intron 6 of 13	ENST00000259895.9	NP_001508.1	Q92759-1A0A1U9X7S4

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
GTF2H4	ENST00000259895.9 link	c.560+51C>A	intron_variant	Intron 6 of 13	1	NM_001517.5	ENSP00000259895.4	Q92759-1
GTF2H4	ENST00000376316.5 link	c.560+51C>A	intron_variant	Intron 6 of 13	5		ENSP00000365493.2	Q92759-1
ENSG00000288473	ENST00000477288.5 link	n.725+51C>A	intron_variant	Intron 6 of 40	2
GTF2H4	ENST00000487746.1 link	n.416+51C>A	intron_variant	Intron 4 of 7	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1314428

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

656296

African (AFR)

AF:

0.00

AC:

AN:

30726

American (AMR)

AF:

0.00

AC:

AN:

37270

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24668

East Asian (EAS)

AF:

0.00

AC:

AN:

37298

South Asian (SAS)

AF:

0.00

AC:

AN:

80260

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5454

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

996816

Other (OTH)

AF:

0.00

AC:

AN:

55318

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

6.1

(source)

DANN

Benign

0.65

PhyloP100

-0.058

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over