Genetic Variant SCHIP1:c.64-136578G>A (chr3-159627865-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.622

Publications

2 publications found

Variant links:

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]

SCHIP1 links:

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]

IQCJ-SCHIP1 links:

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ACMG classification

Classification was made for transcript

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 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCHIP1	NM_014575.4 link	c.64-136578G>A		intron_variant	Intron 1 of 7	ENST00000638749.2	NP_055390.1	P0DPB3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCHIP1	ENST00000638749.2 link	c.64-136578G>A		intron_variant	Intron 1 of 7	1	NM_014575.4	ENSP00000491030.1
IQCJ-SCHIP1	ENST00000485419.7 link	c.292-136578G>A		intron_variant	Intron 4 of 10	2		ENSP00000420182.1		B3KU38-1

Frequencies

GnomAD3 genomes

AF:

0.0212

AC:

3224

AN:

152176

Hom.:

Cov.:

show subpopulations

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.:

Cov.:

AF XY:

0.0213

AC XY:

1586

AN XY:

74454

show subpopulations

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:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00518

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0316

AC:

335

AN:

10600

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00916

AC:

623

AN:

68030

Other (OTH)

AF:

0.0170

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

159

318

477

636

795

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

144

180

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0154

Hom.:

Bravo

AF:

0.0211

Asia WGS

AF:

0.00577

AC:

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

(source)

DANN

Benign

0.61

PhyloP100

-0.62

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over