3-159780660-C-G

Variant names:

• chr3-159780660-C-G
• rs2886623
• NM_014575.4:c.759+15522C>G

Variant summary

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

The NM_014575.4(SCHIP1):​c.759+15522C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.761 in 152,122 control chromosomes in the GnomAD database, including 45,262 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 0.76 (45262 hom., cov: 32)
• Consequence: SCHIP1 NM_014575.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.299
• Publications: 5 publications found

Genes affected

SCHIP1 (HGNC:15678): (schwannomin interacting protein 1) Enables identical protein binding activity. Predicted to be involved in positive regulation of hippo signaling. Predicted to act upstream of or within several processes, including animal organ development; face morphogenesis; and fibroblast migration. Located in several cellular components, including cell junction; cytosol; and nuclear body. [provided by Alliance of Genome Resources, Apr 2022]

IQCJ-SCHIP1 (HGNC:38842): (IQCJ-SCHIP1 readthrough) This locus represents naturally occurring read-through transcription from the neighboring IQ motif containing J (IQCJ) and schwannomin interacting protein 1 (SCHIP1) genes. Alternative splicing results in multiple transcript variants that are composed of in-frame exons from each individual gene. The resulting fusion products are thought to be components of the multimolecular complexes of axon initial segments and nodes of Ranvier, and they may play a role in calcium-mediated responses. [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 (EAS) allele frequency at 95% confidence interval = 0.963 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014575.4. 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
	SCHIP1	NM_014575.4	MANE Select	c.759+15522C>G		intron	N/A	NP_055390.1	P0DPB3-1
	IQCJ-SCHIP1	NM_001197113.2		c.987+15522C>G		intron	N/A	NP_001184042.1	B3KU38-1
	IQCJ-SCHIP1	NM_001197114.2		c.906+15522C>G		intron	N/A	NP_001184043.1	B3KU38-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCHIP1	ENST00000638749.2	TSL:1 MANE Select	c.759+15522C>G		intron	N/A	ENSP00000491030.1	P0DPB3-1
	IQCJ-SCHIP1	ENST00000485419.7	TSL:2	c.987+15522C>G		intron	N/A	ENSP00000420182.1	B3KU38-1
	SCHIP1	ENST00000412423.8	TSL:1	c.720+15561C>G		intron	N/A	ENSP00000400942.2	P0DPB3-2

Frequencies

GnomAD3 genomes AF: 0.761 AC: 115660 AN: 152004 Hom.: 45210 Cov.: 32

Gnomad AFR AF: 0.931

Gnomad AMI AF: 0.658

Gnomad AMR AF: 0.733

Gnomad ASJ AF: 0.766

Gnomad EAS AF: 0.986

Gnomad SAS AF: 0.816

Gnomad FIN AF: 0.658

Gnomad MID AF: 0.778

Gnomad NFE AF: 0.659

Gnomad OTH AF: 0.780

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

GnomAD4 genome AF: 0.761 AC: 115767 AN: 152122 Hom.: 45262 Cov.: 32 AF XY: 0.763 AC XY: 56746 AN XY: 74356

African (AFR) AF: 0.931 AC: 38646 AN: 41510

American (AMR) AF: 0.732 AC: 11198 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.766 AC: 2658 AN: 3468

East Asian (EAS) AF: 0.986 AC: 5109 AN: 5184

South Asian (SAS) AF: 0.815 AC: 3927 AN: 4816

European-Finnish (FIN) AF: 0.658 AC: 6944 AN: 10560

Middle Eastern (MID) AF: 0.762 AC: 224 AN: 294

European-Non Finnish (NFE) AF: 0.659 AC: 44809 AN: 67970

Other (OTH) AF: 0.783 AC: 1652 AN: 2110

Alfa AF: 0.708 Hom.: 4862

Bravo AF: 0.771

Asia WGS AF: 0.916 AC: 3183 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.74
DANN	Benign	0.38
PhyloP100		-0.30
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: rs2886623; hg19: chr3-159498449;