rs11677854

Positions:

• chr2-48664148-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.979-5574C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 151,738 control chromosomes in the GnomAD database, including 2,615 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 (2615 hom., cov: 32)
• Consequence: GTF2A1L NM_006872.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.283

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (SAS) 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.979-5574C>T		intron_variant		ENST00000403751.8	NP_006863.2
STON1-GTF2A1L	NM_001198593.2	c.3091-5574C>T		intron_variant			NP_001185522.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GTF2A1L	ENST00000403751.8	c.979-5574C>T		intron_variant		1	NM_006872.5	ENSP00000384597	P1
GTF2A1L	ENST00000430487.6	c.877-5574C>T		intron_variant		2		ENSP00000387896

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26045 AN: 151620 Hom.: 2612 Cov.: 32

Gnomad AFR AF: 0.0790

Gnomad AMI AF: 0.298

Gnomad AMR AF: 0.188

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.0627

Gnomad SAS AF: 0.239

Gnomad FIN AF: 0.236

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.166

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

GnomAD4 genome AF: 0.172 AC: 26066 AN: 151738 Hom.: 2615 Cov.: 32 AF XY: 0.173 AC XY: 12860 AN XY: 74164

Gnomad4 AFR AF: 0.0791

Gnomad4 AMR AF: 0.188

Gnomad4 ASJ AF: 0.140

Gnomad4 EAS AF: 0.0625

Gnomad4 SAS AF: 0.238

Gnomad4 FIN AF: 0.236

Gnomad4 NFE AF: 0.218

Gnomad4 OTH AF: 0.170

Alfa AF: 0.201 Hom.: 2947

Bravo AF: 0.160

Asia WGS AF: 0.185 AC: 642 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.9
DANN	Benign	0.24

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: rs11677854; hg19: chr2-48891287;