Genetic Variant NM_014575.4:c.64-4739G>A (chr3-159759704-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014575.4(SCHIP1):c.64-4739G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 151,986 control chromosomes in the GnomAD database, including 4,531 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 0.23 ( 4531 hom., cov: 32)

Consequence

SCHIP1
NM_014575.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0870

Publications

6 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:

ENSG00000286913 (HGNC:):

ENSG00000286913 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=-0.54).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.345 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCHIP1	NM_014575.4 link	c.64-4739G>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.64-4739G>A		intron_variant	Intron 1 of 7	1	NM_014575.4	ENSP00000491030.1
IQCJ-SCHIP1	ENST00000485419.7 link	c.292-4739G>A		intron_variant	Intron 4 of 10	2		ENSP00000420182.1		B3KU38-1

Frequencies

GnomAD3 genomes

AF:

0.228

AC:

34564

AN:

151868

Hom.:

4522

Cov.:

show subpopulations

Gnomad AFR

AF:

0.350

Gnomad AMI

AF:

0.138

Gnomad AMR

AF:

0.244

Gnomad ASJ

AF:

0.173

Gnomad EAS

AF:

0.197

Gnomad SAS

AF:

0.287

Gnomad FIN

AF:

0.163

Gnomad MID

AF:

0.373

Gnomad NFE

AF:

0.161

Gnomad OTH

AF:

0.248

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

GnomAD4 genome

AF:

0.228

AC:

34604

AN:

151986

Hom.:

4531

Cov.:

AF XY:

0.227

AC XY:

16840

AN XY:

74278

show subpopulations

African (AFR)

AF:

0.350

AC:

14466

AN:

41382

American (AMR)

AF:

0.244

AC:

3727

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.173

AC:

601

AN:

3472

East Asian (EAS)

AF:

0.197

AC:

1018

AN:

5168

South Asian (SAS)

AF:

0.286

AC:

1379

AN:

4814

European-Finnish (FIN)

AF:

0.163

AC:

1721

AN:

10566

Middle Eastern (MID)

AF:

0.371

AC:

109

AN:

294

European-Non Finnish (NFE)

AF:

0.161

AC:

10925

AN:

67988

Other (OTH)

AF:

0.253

AC:

533

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1296

2592

3888

5184

6480

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

358

716

1074

1432

1790

<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:

0.190

Hom.:

5661

Bravo

AF:

0.236

Asia WGS

AF:

0.240

AC:

832

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Benign

0.77

PhyloP100

-0.087

Mutation Taster

=100/0

polymorphism (auto)

(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