rs7434227

Positions:

• chr3-159627865-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_014575.4(SCHIP1):​c.64-136578G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0212 in 152,294 control chromosomes in the GnomAD database, including 63 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 0.021 (63 hom., cov: 32)
• Consequence: SCHIP1 NM_014575.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.622

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=-0.93).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0212 (3236/152294) while in subpopulation AFR AF= 0.0488 (2027/41570). AF 95% confidence interval is 0.047. There are 63 homozygotes in gnomad4. There are 1586 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 3236 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCHIP1	NM_014575.4	c.64-136578G>A		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.64-136578G>A		intron_variant		1	NM_014575.4	ENSP00000491030.1
IQCJ-SCHIP1	ENST00000485419.7	c.292-136578G>A		intron_variant		2		ENSP00000420182.1

Frequencies

GnomAD3 genomes AF: 0.0212 AC: 3224 AN: 152176 Hom.: 63 Cov.: 32

Gnomad AFR AF: 0.0486

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00989

Gnomad ASJ AF: 0.0101

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00517

Gnomad FIN AF: 0.0316

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00916

Gnomad OTH AF: 0.0167

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

GnomAD4 genome AF: 0.0212 AC: 3236 AN: 152294 Hom.: 63 Cov.: 32 AF XY: 0.0213 AC XY: 1586 AN XY: 74454

Gnomad4 AFR AF: 0.0488

Gnomad4 AMR AF: 0.00981

Gnomad4 ASJ AF: 0.0101

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00518

Gnomad4 FIN AF: 0.0316

Gnomad4 NFE AF: 0.00916

Gnomad4 OTH AF: 0.0170

Alfa AF: 0.0154 Hom.: 10

Bravo AF: 0.0211

Asia WGS AF: 0.00577 AC: 20 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.28
DANN	Benign	0.61

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: rs7434227; hg19: chr3-159345654;