rs1589749

Variant names:

• chr2-48635359-A-G
• rs1589749
• NM_006872.5:c.248-7043A>G

Variant summary

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

The NM_006872.5(GTF2A1L):​c.248-7043A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 152,104 control chromosomes in the GnomAD database, including 2,671 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 0.17 (2671 hom., cov: 32)
• Consequence: GTF2A1L NM_006872.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.330
• Publications: 3 publications found

Genes affected

GTF2A1L (HGNC:30727): (general transcription factor IIA subunit 1 like) The assembly and stability of the RNA polymerase II transcription pre-initiation complex on a eukaryotic core promoter involve the effects of transcription factor IIA (TFIIA) on the interaction between TATA-binding protein (TBP) and DNA. This gene encodes a germ cell-specific counterpart of the large (alpha/beta) subunit of general transcription factor TFIIA that is able to stabilize the binding of TBP to DNA and may be uniquely important to testis biology. Alternative splicing for this locus has been observed and two variants, encoding distinct isoforms, have been identified. Co-transcription of this gene and the neighboring upstream gene generates a rare transcript (SALF), which encodes a fusion protein comprised of sequence sharing identity with each individual gene product. [provided by RefSeq, Mar 2014]

STON1-GTF2A1L (HGNC:30651): (STON1-GTF2A1L readthrough) STON1-GTF2A1L mRNAs are infrequent but naturally occurring read-through products of the neighboring STON1 and GTF2A1L genes. These transcripts encode fusion proteins composed of the vast majority of each of the individual elements, stonin 1 and general transcription factor IIA, 1-like. Alternative splicing results in multiple transcript variants. The significance of these read-through variants and the function of the resulting protein products have not yet been determined. [provided by RefSeq, Oct 2010]

ENSG00000279956 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.244 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GTF2A1L	NM_006872.5	c.248-7043A>G		intron_variant	Intron 3 of 8	ENST00000403751.8	NP_006863.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GTF2A1L	ENST00000403751.8	c.248-7043A>G		intron_variant	Intron 3 of 8	1	NM_006872.5	ENSP00000384597.3
STON1-GTF2A1L	ENST00000394751.5	c.2360-11094A>G		intron_variant	Intron 4 of 7	2		ENSP00000378234.3
ENSG00000279956	ENST00000602369.3	n.*593-2238T>C		intron_variant	Intron 12 of 12	5		ENSP00000473498.1

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26461 AN: 151984 Hom.: 2667 Cov.: 32

Gnomad AFR AF: 0.0845

Gnomad AMI AF: 0.309

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.152

Gnomad EAS AF: 0.0589

Gnomad SAS AF: 0.256

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.167

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

GnomAD4 genome AF: 0.174 AC: 26487 AN: 152104 Hom.: 2671 Cov.: 32 AF XY: 0.176 AC XY: 13074 AN XY: 74350

African (AFR) AF: 0.0847 AC: 3514 AN: 41506

American (AMR) AF: 0.183 AC: 2795 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.152 AC: 527 AN: 3468

East Asian (EAS) AF: 0.0586 AC: 302 AN: 5152

South Asian (SAS) AF: 0.256 AC: 1236 AN: 4824

European-Finnish (FIN) AF: 0.233 AC: 2465 AN: 10580

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.220 AC: 14964 AN: 67974

Other (OTH) AF: 0.171 AC: 362 AN: 2114

Alfa AF: 0.198 Hom.: 768

Bravo AF: 0.162

Asia WGS AF: 0.193 AC: 671 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.6
DANN	Benign	0.63
PhyloP100		0.33
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: rs1589749; hg19: chr2-48862498;