rs1464729

Positions:

• chr2-48678817-C-T

Variant summary

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

The NM_006872.5(GTF2A1L):​c.1330-518C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.662 in 151,710 control chromosomes in the GnomAD database, including 33,694 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 0.66 (33694 hom., cov: 30)
• Consequence: GTF2A1L NM_006872.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.408

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.907 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GTF2A1L	NM_006872.5	c.1330-518C>T		intron_variant		ENST00000403751.8	NP_006863.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GTF2A1L	ENST00000403751.8	c.1330-518C>T		intron_variant		1	NM_006872.5	ENSP00000384597.3
STON1-GTF2A1L	ENST00000394754.5	c.3442-518C>T		intron_variant		1		ENSP00000378236.1
ENSG00000279956	ENST00000602369.3	n.*221-10152G>A		intron_variant		5		ENSP00000473498.1

Frequencies

GnomAD3 genomes AF: 0.662 AC: 100290 AN: 151592 Hom.: 33670 Cov.: 30

Gnomad AFR AF: 0.561

Gnomad AMI AF: 0.629

Gnomad AMR AF: 0.719

Gnomad ASJ AF: 0.777

Gnomad EAS AF: 0.929

Gnomad SAS AF: 0.687

Gnomad FIN AF: 0.676

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.679

Gnomad OTH AF: 0.690

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

GnomAD4 genome AF: 0.662 AC: 100365 AN: 151710 Hom.: 33694 Cov.: 30 AF XY: 0.666 AC XY: 49365 AN XY: 74144

Gnomad4 AFR AF: 0.561

Gnomad4 AMR AF: 0.719

Gnomad4 ASJ AF: 0.777

Gnomad4 EAS AF: 0.929

Gnomad4 SAS AF: 0.688

Gnomad4 FIN AF: 0.676

Gnomad4 NFE AF: 0.679

Gnomad4 OTH AF: 0.688

Alfa AF: 0.676 Hom.: 16223

Bravo AF: 0.665

Asia WGS AF: 0.757 AC: 2634 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	8.6
DANN	Benign	0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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: rs1464729; hg19: chr2-48905956;