rs9812406

Positions:

• chr3-159695948-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014575.4(SCHIP1):​c.64-68495C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 151,878 control chromosomes in the GnomAD database, including 9,415 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 0.29 (9415 hom., cov: 32)
• Consequence: SCHIP1 NM_014575.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.818

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.594 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCHIP1	NM_014575.4	c.64-68495C>T		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.64-68495C>T		intron_variant		1	NM_014575.4	ENSP00000491030.1
IQCJ-SCHIP1	ENST00000485419.7	c.292-68495C>T		intron_variant		2		ENSP00000420182.1

Frequencies

GnomAD3 genomes AF: 0.289 AC: 43883 AN: 151760 Hom.: 9370 Cov.: 32

Gnomad AFR AF: 0.599

Gnomad AMI AF: 0.274

Gnomad AMR AF: 0.288

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.225

Gnomad SAS AF: 0.228

Gnomad FIN AF: 0.106

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.282

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

GnomAD4 genome AF: 0.290 AC: 43994 AN: 151878 Hom.: 9415 Cov.: 32 AF XY: 0.286 AC XY: 21222 AN XY: 74232

Gnomad4 AFR AF: 0.600

Gnomad4 AMR AF: 0.288

Gnomad4 ASJ AF: 0.140

Gnomad4 EAS AF: 0.226

Gnomad4 SAS AF: 0.227

Gnomad4 FIN AF: 0.106

Gnomad4 NFE AF: 0.147

Gnomad4 OTH AF: 0.288

Alfa AF: 0.172 Hom.: 5744

Bravo AF: 0.316

Asia WGS AF: 0.287 AC: 998 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.6
DANN	Benign	0.64

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: rs9812406; hg19: chr3-159413737;