rs11685904

chr2-48634765-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.248-7637C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 152,176 control chromosomes in the GnomAD database, including 2,471 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 0.16 (2471 hom., cov: 32)
• Consequence: GTF2A1L NM_006872.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.742

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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.241 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GTF2A1L	NM_006872.5	c.248-7637C>T		intron_variant		ENST00000403751.8
STON1-GTF2A1L	NM_001198593.2	c.2360-7637C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GTF2A1L	ENST00000403751.8	c.248-7637C>T		intron_variant		1	NM_006872.5	P1

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24552 AN: 152060 Hom.: 2469 Cov.: 32

Gnomad AFR AF: 0.0518

Gnomad AMI AF: 0.299

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.139

Gnomad EAS AF: 0.0579

Gnomad SAS AF: 0.253

Gnomad FIN AF: 0.232

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.215

Gnomad OTH AF: 0.154

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

GnomAD4 genome AF: 0.161 AC: 24559 AN: 152176 Hom.: 2471 Cov.: 32 AF XY: 0.163 AC XY: 12160 AN XY: 74382

Gnomad4 AFR AF: 0.0517

Gnomad4 AMR AF: 0.178

Gnomad4 ASJ AF: 0.139

Gnomad4 EAS AF: 0.0576

Gnomad4 SAS AF: 0.253

Gnomad4 FIN AF: 0.232

Gnomad4 NFE AF: 0.215

Gnomad4 OTH AF: 0.157

Alfa AF: 0.191 Hom.: 720

Bravo AF: 0.149

Asia WGS AF: 0.186 AC: 645 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	1.2
Dann	Benign	0.44

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: rs11685904; hg19: chr2-48861904;