2-48758468-C-T

Variant names:

• chr2-48758468-C-T
• rs4245818
• NM_001198593.2:c.3442-17812C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001198593.2(STON1-GTF2A1L):​c.3442-17812C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.754 in 152,144 control chromosomes in the GnomAD database, including 43,858 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 0.75 (43858 hom., cov: 33)
• Consequence: STON1-GTF2A1L NM_001198593.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.913
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.877 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STON1-GTF2A1L	NM_001198593.2	c.3442-17812C>T		intron_variant	Intron 10 of 10		NP_001185522.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STON1-GTF2A1L	ENST00000402114.6	c.3442-17812C>T		intron_variant	Intron 10 of 10	2		ENSP00000385701.1

Frequencies

GnomAD3 genomes AF: 0.754 AC: 114616 AN: 152024 Hom.: 43803 Cov.: 33

Gnomad AFR AF: 0.884

Gnomad AMI AF: 0.794

Gnomad AMR AF: 0.788

Gnomad ASJ AF: 0.644

Gnomad EAS AF: 0.662

Gnomad SAS AF: 0.664

Gnomad FIN AF: 0.607

Gnomad MID AF: 0.615

Gnomad NFE AF: 0.709

Gnomad OTH AF: 0.753

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

GnomAD4 genome AF: 0.754 AC: 114731 AN: 152144 Hom.: 43858 Cov.: 33 AF XY: 0.748 AC XY: 55596 AN XY: 74356

African (AFR) AF: 0.884 AC: 36717 AN: 41522

American (AMR) AF: 0.789 AC: 12061 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.644 AC: 2235 AN: 3470

East Asian (EAS) AF: 0.662 AC: 3423 AN: 5168

South Asian (SAS) AF: 0.665 AC: 3205 AN: 4822

European-Finnish (FIN) AF: 0.607 AC: 6415 AN: 10564

Middle Eastern (MID) AF: 0.613 AC: 179 AN: 292

European-Non Finnish (NFE) AF: 0.709 AC: 48185 AN: 67988

Other (OTH) AF: 0.751 AC: 1587 AN: 2112

Alfa AF: 0.741 Hom.: 15272

Bravo AF: 0.773

Asia WGS AF: 0.668 AC: 2321 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.39
DANN	Benign	0.72
PhyloP100		-0.91
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs4245818; hg19: chr2-48985607;