chr13-45252085-G-A

Variant names:

• chr13-45252085-G-A
• rs10507534
• NM_004128.3:c.387-786G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004128.3(GTF2F2):​c.387-786G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.326 in 152,070 control chromosomes in the GnomAD database, including 10,310 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 0.33 (10310 hom., cov: 32)
• Consequence: GTF2F2 NM_004128.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.284
• Publications: 2 publications found

Genes affected

GTF2F2 (HGNC:4653): (general transcription factor IIF subunit 2) Predicted to enable RNA polymerase II general transcription initiation factor activity. Involved in transcription by RNA polymerase II. Located in microtubule cytoskeleton and nucleoplasm. Part of transcription preinitiation complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.582 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GTF2F2	NM_004128.3	c.387-786G>A		intron_variant	Intron 5 of 7	ENST00000340473.8	NP_004119.1
GTF2F2	XM_011535052.4	c.465-786G>A		intron_variant	Intron 6 of 8		XP_011533354.1
GTF2F2	XM_017020551.2	c.87-786G>A		intron_variant	Intron 2 of 4		XP_016876040.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GTF2F2	ENST00000340473.8	c.387-786G>A		intron_variant	Intron 5 of 7	1	NM_004128.3	ENSP00000340823.6

Frequencies

GnomAD3 genomes AF: 0.326 AC: 49562 AN: 151952 Hom.: 10298 Cov.: 32

Gnomad AFR AF: 0.588

Gnomad AMI AF: 0.240

Gnomad AMR AF: 0.235

Gnomad ASJ AF: 0.228

Gnomad EAS AF: 0.0610

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.244

Gnomad OTH AF: 0.320

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

GnomAD4 genome AF: 0.326 AC: 49606 AN: 152070 Hom.: 10310 Cov.: 32 AF XY: 0.319 AC XY: 23736 AN XY: 74328

African (AFR) AF: 0.588 AC: 24373 AN: 41466

American (AMR) AF: 0.234 AC: 3574 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.228 AC: 790 AN: 3468

East Asian (EAS) AF: 0.0609 AC: 315 AN: 5170

South Asian (SAS) AF: 0.172 AC: 827 AN: 4820

European-Finnish (FIN) AF: 0.204 AC: 2161 AN: 10574

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.244 AC: 16612 AN: 67980

Other (OTH) AF: 0.316 AC: 666 AN: 2108

Alfa AF: 0.309 Hom.: 2157

Bravo AF: 0.340

Asia WGS AF: 0.141 AC: 492 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.0
DANN	Benign	0.084
PhyloP100		0.28
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10507534; hg19: chr13-45826220;