rs11677854

Variant names:

• chr2-48664148-C-T
• rs11677854
• NM_006872.5:c.979-5574C>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.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
• Publications: 2 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=-1.02).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.227 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006872.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GTF2A1L	NM_006872.5	MANE Select	c.979-5574C>T		intron	N/A	NP_006863.2
	STON1-GTF2A1L	NM_172311.3		c.3091-5574C>T		intron	N/A	NP_758515.1	Q53S48
	STON1-GTF2A1L	NM_001198593.2		c.3091-5574C>T		intron	N/A	NP_001185522.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GTF2A1L	ENST00000403751.8	TSL:1 MANE Select	c.979-5574C>T		intron	N/A	ENSP00000384597.3	Q9UNN4-1
	STON1-GTF2A1L	ENST00000394754.5	TSL:1	c.3091-5574C>T		intron	N/A	ENSP00000378236.1	Q53S48
	STON1-GTF2A1L	ENST00000394751.5	TSL:2	c.2950-5574C>T		intron	N/A	ENSP00000378234.3

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

African (AFR) AF: 0.0791 AC: 3274 AN: 41404

American (AMR) AF: 0.188 AC: 2871 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.140 AC: 486 AN: 3468

East Asian (EAS) AF: 0.0625 AC: 322 AN: 5152

South Asian (SAS) AF: 0.238 AC: 1146 AN: 4812

European-Finnish (FIN) AF: 0.236 AC: 2464 AN: 10424

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

European-Non Finnish (NFE) AF: 0.218 AC: 14834 AN: 67914

Other (OTH) AF: 0.170 AC: 359 AN: 2106

Alfa AF: 0.200 Hom.: 3452

Bravo AF: 0.160

Asia WGS AF: 0.185 AC: 642 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.9
DANN	Benign	0.24
PhyloP100		-0.28
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: rs11677854; hg19: chr2-48891287;