rs7434227

Variant names:

• chr3-159627865-G-A
• rs7434227
• NM_014575.4:c.64-136578G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001197113.2(IQCJ-SCHIP1):​c.292-136578G>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: IQCJ-SCHIP1 NM_001197113.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.622
• Publications: 2 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=-0.93).
• 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 63 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001197113.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCHIP1	NM_014575.4	MANE Select	c.64-136578G>A		intron	N/A	NP_055390.1
	IQCJ-SCHIP1	NM_001197113.2		c.292-136578G>A		intron	N/A	NP_001184042.1
	IQCJ-SCHIP1	NM_001197114.2		c.211-136578G>A		intron	N/A	NP_001184043.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCHIP1	ENST00000638749.2	TSL:1 MANE Select	c.64-136578G>A		intron	N/A	ENSP00000491030.1
	IQCJ-SCHIP1	ENST00000485419.7	TSL:2	c.292-136578G>A		intron	N/A	ENSP00000420182.1
	SCHIP1	ENST00000412423.8	TSL:1	c.64-136578G>A		intron	N/A	ENSP00000400942.2

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

African (AFR) AF: 0.0488 AC: 2027 AN: 41570

American (AMR) AF: 0.00981 AC: 150 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0101 AC: 35 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00518 AC: 25 AN: 4828

European-Finnish (FIN) AF: 0.0316 AC: 335 AN: 10600

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.00916 AC: 623 AN: 68030

Other (OTH) AF: 0.0170 AC: 36 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.28
DANN	Benign	0.61
PhyloP100		-0.62
Mutation Taster		=100/0	polymorphism

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: rs7434227; hg19: chr3-159345654;