3-159541502-T-C

Variant names:

• chr3-159541502-T-C
• rs2222328
• NM_014575.4:c.64-222941T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_014575.4(SCHIP1):​c.64-222941T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 152,028 control chromosomes in the GnomAD database, including 2,540 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 (2540 hom., cov: 32)
• Consequence: SCHIP1 NM_014575.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.588
• Publications: 9 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.34 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCHIP1	NM_014575.4	c.64-222941T>C		intron_variant	Intron 1 of 7	ENST00000638749.2	NP_055390.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCHIP1	ENST00000638749.2	c.64-222941T>C		intron_variant	Intron 1 of 7	1	NM_014575.4	ENSP00000491030.1
IQCJ-SCHIP1	ENST00000485419.7	c.292-222941T>C		intron_variant	Intron 4 of 10	2		ENSP00000420182.1

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26425 AN: 151910 Hom.: 2541 Cov.: 32

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.0626

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.211

Gnomad EAS AF: 0.304

Gnomad SAS AF: 0.354

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.173

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

GnomAD4 genome AF: 0.174 AC: 26436 AN: 152028 Hom.: 2540 Cov.: 32 AF XY: 0.182 AC XY: 13534 AN XY: 74290

African (AFR) AF: 0.117 AC: 4870 AN: 41514

American (AMR) AF: 0.205 AC: 3129 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.211 AC: 732 AN: 3468

East Asian (EAS) AF: 0.304 AC: 1570 AN: 5162

South Asian (SAS) AF: 0.354 AC: 1705 AN: 4822

European-Finnish (FIN) AF: 0.223 AC: 2354 AN: 10578

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.171 AC: 11588 AN: 67942

Other (OTH) AF: 0.175 AC: 368 AN: 2108

Alfa AF: 0.173 Hom.: 7540

Bravo AF: 0.165

Asia WGS AF: 0.346 AC: 1203 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	15
DANN	Benign	0.76
PhyloP100		0.59
Mutation Taster		=99/1	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: rs2222328; hg19: chr3-159259291;