NM_006872.5:c.248-7637C>T

Variant names:

• chr2-48634765-C-T
• rs11685904
• NM_006872.5:c.248-7637C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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=-0.92).
• 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 rank	MANE	Protein	UniProt
GTF2A1L	NM_006872.5	c.248-7637C>T		intron_variant	Intron 3 of 8	ENST00000403751.8	NP_006863.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GTF2A1L	ENST00000403751.8	c.248-7637C>T		intron_variant	Intron 3 of 8	1	NM_006872.5	ENSP00000384597.3
STON1-GTF2A1L	ENST00000394751.5	c.2360-11688C>T		intron_variant	Intron 4 of 7	2		ENSP00000378234.3
ENSG00000279956	ENST00000602369.3	n.*593-1644G>A		intron_variant	Intron 12 of 12	5		ENSP00000473498.1

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

African (AFR) AF: 0.0517 AC: 2146 AN: 41542

American (AMR) AF: 0.178 AC: 2715 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.139 AC: 481 AN: 3470

East Asian (EAS) AF: 0.0576 AC: 299 AN: 5190

South Asian (SAS) AF: 0.253 AC: 1218 AN: 4822

European-Finnish (FIN) AF: 0.232 AC: 2453 AN: 10582

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

European-Non Finnish (NFE) AF: 0.215 AC: 14605 AN: 67976

Other (OTH) AF: 0.157 AC: 331 AN: 2106

Alfa AF: 0.189 Hom.: 730

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
PhyloP100		-0.74
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: rs11685904; hg19: chr2-48861904;