2-48672377-C-G

Variant names:

• chr2-48672377-C-G
• rs13024367
• NM_006872.5:c.1329+697C>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.1329+697C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 152,042 control chromosomes in the GnomAD database, including 2,616 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 (2616 hom., cov: 32)
• Consequence: GTF2A1L NM_006872.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.273
• Publications: 1 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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.23 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GTF2A1L	NM_006872.5	c.1329+697C>G		intron_variant	Intron 8 of 8	ENST00000403751.8	NP_006863.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GTF2A1L	ENST00000403751.8	c.1329+697C>G		intron_variant	Intron 8 of 8	1	NM_006872.5	ENSP00000384597.3
STON1-GTF2A1L	ENST00000394751.5	c.3300+697C>G		intron_variant	Intron 7 of 7	2		ENSP00000378234.3
ENSG00000279956	ENST00000602369.3	n.*221-3712G>C		intron_variant	Intron 9 of 12	5		ENSP00000473498.1

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25262 AN: 151924 Hom.: 2614 Cov.: 32

Gnomad AFR AF: 0.0522

Gnomad AMI AF: 0.298

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.142

Gnomad EAS AF: 0.0707

Gnomad SAS AF: 0.242

Gnomad FIN AF: 0.237

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.221

Gnomad OTH AF: 0.161

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

GnomAD4 genome AF: 0.166 AC: 25268 AN: 152042 Hom.: 2616 Cov.: 32 AF XY: 0.168 AC XY: 12484 AN XY: 74344

African (AFR) AF: 0.0520 AC: 2159 AN: 41494

American (AMR) AF: 0.189 AC: 2891 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.142 AC: 487 AN: 3434

East Asian (EAS) AF: 0.0704 AC: 365 AN: 5182

South Asian (SAS) AF: 0.241 AC: 1161 AN: 4814

European-Finnish (FIN) AF: 0.237 AC: 2505 AN: 10578

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.221 AC: 15043 AN: 67960

Other (OTH) AF: 0.164 AC: 347 AN: 2114

Alfa AF: 0.187 Hom.: 374

Bravo AF: 0.154

Asia WGS AF: 0.193 AC: 668 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.2
DANN	Benign	0.64
PhyloP100		0.27
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: rs13024367; hg19: chr2-48899516;