rs1996970

Variant names:

• chr2-48571344-G-C
• rs1996970
• NM_006873.4:c.-47-9243G>C

Variant summary

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

The NM_006873.4(STON1):​c.-47-9243G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.618 in 151,992 control chromosomes in the GnomAD database, including 29,431 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 0.62 (29431 hom., cov: 31)
• Consequence: STON1 NM_006873.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09
• Publications: 4 publications found

Genes affected

STON1 (HGNC:17003): (stonin 1) Endocytosis of cell surface proteins is mediated by a complex molecular machinery that assembles on the inner surface of the plasma membrane. This gene encodes one of two human homologs of the Drosophila melanogaster stoned B protein. This protein is related to components of the endocytic machinery and exhibits a modular structure consisting of an N-terminal proline-rich domain, a central region of homology specific to the human stoned B-like proteins, and a C-terminal region homologous to the mu subunits of adaptor protein (AP) complexes. Read-through transcription of this gene into the neighboring downstream gene, which encodes TFIIA-alpha/beta-like factor, generates a transcript (SALF), which encodes a fusion protein comprised of sequence sharing identity with each individual gene product. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2010]

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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.645 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STON1	NM_006873.4	c.-47-9243G>C		intron_variant	Intron 1 of 3	ENST00000404752.6	NP_006864.2
STON1-GTF2A1L	NM_172311.3	c.-48+2258G>C		intron_variant	Intron 1 of 10		NP_758515.1
STON1-GTF2A1L	NM_001198593.2	c.-47-9243G>C		intron_variant	Intron 1 of 10		NP_001185522.1
STON1	NM_001198595.2	c.-47-9243G>C		intron_variant	Intron 2 of 4		NP_001185524.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STON1	ENST00000404752.6	c.-47-9243G>C		intron_variant	Intron 1 of 3	1	NM_006873.4	ENSP00000385273.1

Frequencies

GnomAD3 genomes AF: 0.618 AC: 93884 AN: 151876 Hom.: 29408 Cov.: 31

Gnomad AFR AF: 0.601

Gnomad AMI AF: 0.680

Gnomad AMR AF: 0.526

Gnomad ASJ AF: 0.533

Gnomad EAS AF: 0.421

Gnomad SAS AF: 0.498

Gnomad FIN AF: 0.794

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.650

Gnomad OTH AF: 0.586

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

GnomAD4 genome AF: 0.618 AC: 93967 AN: 151992 Hom.: 29431 Cov.: 31 AF XY: 0.618 AC XY: 45895 AN XY: 74294

African (AFR) AF: 0.602 AC: 24930 AN: 41438

American (AMR) AF: 0.527 AC: 8044 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.533 AC: 1851 AN: 3472

East Asian (EAS) AF: 0.420 AC: 2164 AN: 5156

South Asian (SAS) AF: 0.498 AC: 2394 AN: 4810

European-Finnish (FIN) AF: 0.794 AC: 8403 AN: 10580

Middle Eastern (MID) AF: 0.503 AC: 148 AN: 294

European-Non Finnish (NFE) AF: 0.650 AC: 44177 AN: 67942

Other (OTH) AF: 0.585 AC: 1237 AN: 2114

Alfa AF: 0.644 Hom.: 3980

Bravo AF: 0.595

Asia WGS AF: 0.472 AC: 1641 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.52
DANN	Benign	0.66
PhyloP100		-1.1
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: rs1996970; hg19: chr2-48798483;