3-159541669-T-C

Position:

• chr3-159541669-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCHIP1	NM_014575.4	c.64-222774T>C		intron_variant		ENST00000638749.2	NP_055390.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IQCJ-SCHIP1	ENST00000638749.2	c.64-222774T>C		intron_variant		1	NM_014575.4	ENSP00000491030.1
IQCJ-SCHIP1	ENST00000485419.7	c.292-222774T>C		intron_variant		2		ENSP00000420182.1

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

Gnomad4 AFR AF: 0.379

Gnomad4 AMR AF: 0.311

Gnomad4 ASJ AF: 0.295

Gnomad4 EAS AF: 0.430

Gnomad4 SAS AF: 0.515

Gnomad4 FIN AF: 0.328

Gnomad4 NFE AF: 0.295

Gnomad4 OTH AF: 0.332

Alfa AF: 0.312 Hom.: 4229

Bravo AF: 0.329

Asia WGS AF: 0.527 AC: 1831 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.5
DANN	Benign	0.84

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

Publications

LitVar

Other links and lift over

dbSNP: rs1402276; hg19: chr3-159259458;