3-159784974-C-T

Variant names:

• chr3-159784974-C-T
• rs3863075
• NM_014575.4:c.759+19836C>T

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+19836C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.662 in 152,120 control chromosomes in the GnomAD database, including 33,793 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 0.66 (33793 hom., cov: 33)
• Consequence: SCHIP1 NM_014575.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.530
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.963 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCHIP1	NM_014575.4	c.759+19836C>T		intron_variant	Intron 2 of 7	ENST00000638749.2	NP_055390.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCHIP1	ENST00000638749.2	c.759+19836C>T		intron_variant	Intron 2 of 7	1	NM_014575.4	ENSP00000491030.1
IQCJ-SCHIP1	ENST00000485419.7	c.987+19836C>T		intron_variant	Intron 5 of 10	2		ENSP00000420182.1

Frequencies

GnomAD3 genomes AF: 0.662 AC: 100585 AN: 152002 Hom.: 33776 Cov.: 33

Gnomad AFR AF: 0.593

Gnomad AMI AF: 0.658

Gnomad AMR AF: 0.690

Gnomad ASJ AF: 0.752

Gnomad EAS AF: 0.986

Gnomad SAS AF: 0.808

Gnomad FIN AF: 0.657

Gnomad MID AF: 0.747

Gnomad NFE AF: 0.656

Gnomad OTH AF: 0.705

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

GnomAD4 genome AF: 0.662 AC: 100652 AN: 152120 Hom.: 33793 Cov.: 33 AF XY: 0.667 AC XY: 49621 AN XY: 74376

African (AFR) AF: 0.593 AC: 24609 AN: 41472

American (AMR) AF: 0.690 AC: 10539 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.752 AC: 2611 AN: 3472

East Asian (EAS) AF: 0.986 AC: 5113 AN: 5188

South Asian (SAS) AF: 0.808 AC: 3896 AN: 4824

European-Finnish (FIN) AF: 0.657 AC: 6943 AN: 10566

Middle Eastern (MID) AF: 0.731 AC: 215 AN: 294

European-Non Finnish (NFE) AF: 0.656 AC: 44630 AN: 67994

Other (OTH) AF: 0.708 AC: 1496 AN: 2114

Alfa AF: 0.664 Hom.: 18749

Bravo AF: 0.656

Asia WGS AF: 0.888 AC: 3087 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.44
DANN	Benign	0.54
PhyloP100		-0.53
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: rs3863075; hg19: chr3-159502763;