2-48757252-C-T

Position:

• chr2-48757252-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001198593.2(STON1-GTF2A1L):​c.3442-19028C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.425 in 151,972 control chromosomes in the GnomAD database, including 14,224 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 0.43 (14224 hom., cov: 32)
• Consequence: STON1-GTF2A1L NM_001198593.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.173

Genes affected

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.475 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STON1-GTF2A1L	NM_001198593.2	c.3442-19028C>T		intron_variant			NP_001185522.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STON1-GTF2A1L	ENST00000402114.6	c.3442-19028C>T		intron_variant		2		ENSP00000385701.1

Frequencies

GnomAD3 genomes AF: 0.425 AC: 64563 AN: 151854 Hom.: 14216 Cov.: 32

Gnomad AFR AF: 0.350

Gnomad AMI AF: 0.533

Gnomad AMR AF: 0.482

Gnomad ASJ AF: 0.434

Gnomad EAS AF: 0.337

Gnomad SAS AF: 0.187

Gnomad FIN AF: 0.425

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.480

Gnomad OTH AF: 0.439

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

GnomAD4 genome AF: 0.425 AC: 64595 AN: 151972 Hom.: 14224 Cov.: 32 AF XY: 0.417 AC XY: 30979 AN XY: 74274

Gnomad4 AFR AF: 0.350

Gnomad4 AMR AF: 0.482

Gnomad4 ASJ AF: 0.434

Gnomad4 EAS AF: 0.338

Gnomad4 SAS AF: 0.187

Gnomad4 FIN AF: 0.425

Gnomad4 NFE AF: 0.480

Gnomad4 OTH AF: 0.433

Alfa AF: 0.467 Hom.: 32420

Bravo AF: 0.431

Asia WGS AF: 0.260 AC: 905 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.4
DANN	Benign	0.58

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2301267; hg19: chr2-48984391;