NM_014575.4:c.64-222774T>C

Variant names:

• chr3-159541669-T-C
• rs1402276
• NM_014575.4:c.64-222774T>C

Variant summary

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

The NM_014575.4(SCHIP1):​c.64-222774T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 151,906 control chromosomes in the GnomAD database, including 8,675 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 0.33 (8675 hom., cov: 32)
• Consequence: SCHIP1 NM_014575.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.518
• Publications: 4 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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.498 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCHIP1	NM_014575.4	MANE Select	c.64-222774T>C		intron	N/A	NP_055390.1
	IQCJ-SCHIP1	NM_001197113.2		c.292-222774T>C		intron	N/A	NP_001184042.1
	IQCJ-SCHIP1	NM_001197114.2		c.211-222774T>C		intron	N/A	NP_001184043.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCHIP1	ENST00000638749.2	TSL:1 MANE Select	c.64-222774T>C		intron	N/A	ENSP00000491030.1
	IQCJ-SCHIP1	ENST00000485419.7	TSL:2	c.292-222774T>C		intron	N/A	ENSP00000420182.1
	SCHIP1	ENST00000412423.8	TSL:1	c.64-222774T>C		intron	N/A	ENSP00000400942.2

Frequencies

GnomAD3 genomes AF: 0.334 AC: 50759 AN: 151788 Hom.: 8649 Cov.: 32

Gnomad AFR AF: 0.379

Gnomad AMI AF: 0.353

Gnomad AMR AF: 0.311

Gnomad ASJ AF: 0.295

Gnomad EAS AF: 0.431

Gnomad SAS AF: 0.517

Gnomad FIN AF: 0.328

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.295

Gnomad OTH AF: 0.326

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

GnomAD4 genome AF: 0.335 AC: 50822 AN: 151906 Hom.: 8675 Cov.: 32 AF XY: 0.342 AC XY: 25358 AN XY: 74230

African (AFR) AF: 0.379 AC: 15720 AN: 41442

American (AMR) AF: 0.311 AC: 4739 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.295 AC: 1024 AN: 3468

East Asian (EAS) AF: 0.430 AC: 2218 AN: 5154

South Asian (SAS) AF: 0.515 AC: 2481 AN: 4816

European-Finnish (FIN) AF: 0.328 AC: 3467 AN: 10574

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.295 AC: 20047 AN: 67902

Other (OTH) AF: 0.332 AC: 700 AN: 2108

Alfa AF: 0.309 Hom.: 5544

Bravo AF: 0.329

Asia WGS AF: 0.527 AC: 1831 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.5
DANN	Benign	0.84
PhyloP100		-0.52
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: rs1402276; hg19: chr3-159259458;