2-48672668-C-T

Position:

• chr2-48672668-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.1329+988C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0909 in 152,042 control chromosomes in the GnomAD database, including 954 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 0.091 (954 hom., cov: 32)
• Consequence: GTF2A1L NM_006872.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.124

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=-0.69).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.227 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GTF2A1L	NM_006872.5	c.1329+988C>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.1329+988C>T		intron_variant		1	NM_006872.5	ENSP00000384597.3
STON1-GTF2A1L	ENST00000394754.5	c.3441+988C>T		intron_variant		1		ENSP00000378236.1
ENSG00000279956	ENST00000602369.3	n.*221-4003G>A		intron_variant		5		ENSP00000473498.1

Frequencies

GnomAD3 genomes AF: 0.0909 AC: 13816 AN: 151924 Hom.: 950 Cov.: 32

Gnomad AFR AF: 0.0211

Gnomad AMI AF: 0.0967

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.0309

Gnomad EAS AF: 0.237

Gnomad SAS AF: 0.0237

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.0751

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

GnomAD4 genome AF: 0.0909 AC: 13821 AN: 152042 Hom.: 954 Cov.: 32 AF XY: 0.0939 AC XY: 6975 AN XY: 74310

Gnomad4 AFR AF: 0.0211

Gnomad4 AMR AF: 0.161

Gnomad4 ASJ AF: 0.0309

Gnomad4 EAS AF: 0.238

Gnomad4 SAS AF: 0.0233

Gnomad4 FIN AF: 0.170

Gnomad4 NFE AF: 0.103

Gnomad4 OTH AF: 0.0729

Alfa AF: 0.0875 Hom.: 834

Bravo AF: 0.0912

Asia WGS AF: 0.107 AC: 372 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	3.4
DANN	Benign	0.76

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: rs11682325; hg19: chr2-48899807;