rs2174769

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_024700.4(SNIP1):c.328-3T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.834 in 1,578,512 control chromosomes in the GnomAD database, including 556,525 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.75 ( 44743 hom., cov: 32)

Exomes 𝑓: 0.84 ( 511782 hom. )

Consequence

SNIP1
NM_024700.4 splice_region, intron

Scores

Splicing: ADA: 0.00007978

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.792

Publications

16 publications found

Variant links:

Genes affected

SNIP1 (HGNC:30587): (Smad nuclear interacting protein 1) This gene encodes a protein that contains a coiled-coil motif and C-terminal forkhead-associated (FHA) domain. The encoded protein functions as a transcriptional coactivator that increases c-Myc activity and inhibits transforming growth factor beta (TGF-beta) and nuclear factor kappa-B (NF-kB) signaling. The encoded protein also regulates the stability of cyclin D1 mRNA, and may play a role in cell proliferation and cancer progression. Mutations in this gene are a cause of psychomotor retardation, epilepsy, and craniofacial dysmorphism (PMRED). [provided by RefSeq, Mar 2012]

SNIP1 Gene-Disease associations (from GenCC):

psychomotor retardation, epilepsy, and craniofacial dysmorphism
Inheritance: Unknown, AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Illumina, G2P

SNIP1 links:

ENSG00000307694 (HGNC:):

ENSG00000307694 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 1-37540758-A-G is Benign according to our data. Variant chr1-37540758-A-G is described in ClinVar as Benign. ClinVar VariationId is 1167876.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.938 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNIP1	NM_024700.4 link	c.328-3T>C		splice_region_variant, intron_variant	Intron 2 of 3	ENST00000296215.8	NP_078976.2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
SNIP1	ENST00000296215.8 link	c.328-3T>C	splice_region_variant, intron_variant	Intron 2 of 3	1	NM_024700.4	ENSP00000296215.5
SNIP1	ENST00000638725.1 link	n.837T>C	non_coding_transcript_exon_variant	Exon 1 of 2	2
ENSG00000307694	ENST00000827919.1 link	n.939A>G	non_coding_transcript_exon_variant	Exon 3 of 3
SNIP1	ENST00000468040.2 link	n.*102-3T>C	splice_region_variant, intron_variant	Intron 3 of 4	5		ENSP00000492185.1

Frequencies

GnomAD3 genomes

AF:

0.747

AC:

113480

AN:

152002

Hom.:

44708

Cov.:

show subpopulations

Gnomad AFR

AF:

0.474

Gnomad AMI

AF:

0.752

Gnomad AMR

AF:

0.835

Gnomad ASJ

AF:

0.755

Gnomad EAS

AF:

0.961

Gnomad SAS

AF:

0.713

Gnomad FIN

AF:

0.899

Gnomad MID

AF:

0.652

Gnomad NFE

AF:

0.854

Gnomad OTH

AF:

0.768

GnomAD2 exomes

AF:

0.820

AC:

191782

AN:

233950

AF XY:

0.818

show subpopulations

Gnomad AFR exome

AF:

0.466

Gnomad AMR exome

AF:

0.883

Gnomad ASJ exome

AF:

0.767

Gnomad EAS exome

AF:

0.962

Gnomad FIN exome

AF:

0.896

Gnomad NFE exome

AF:

0.848

Gnomad OTH exome

AF:

0.825

GnomAD4 exome

AF:

0.843

AC:

1203034

AN:

1426394

Hom.:

511782

Cov.:

AF XY:

0.840

AC XY:

592217

AN XY:

705402

show subpopulations

African (AFR)

AF:

0.454

AC:

14759

AN:

32518

American (AMR)

AF:

0.878

AC:

35874

AN:

40872

Ashkenazi Jewish (ASJ)

AF:

0.768

AC:

18953

AN:

24688

East Asian (EAS)

AF:

0.954

AC:

37331

AN:

39148

South Asian (SAS)

AF:

0.719

AC:

60470

AN:

84160

European-Finnish (FIN)

AF:

0.892

AC:

43103

AN:

48334

Middle Eastern (MID)

AF:

0.731

AC:

4105

AN:

5612

European-Non Finnish (NFE)

AF:

0.861

AC:

940225

AN:

1092260

Other (OTH)

AF:

0.820

AC:

48214

AN:

58802

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

10248

20496

30744

40992

51240

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21120

42240

63360

84480

105600

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.747

AC:

113562

AN:

152118

Hom.:

44743

Cov.:

AF XY:

0.749

AC XY:

55723

AN XY:

74380

show subpopulations

African (AFR)

AF:

0.475

AC:

19679

AN:

41452

American (AMR)

AF:

0.835

AC:

12761

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.755

AC:

2619

AN:

3470

East Asian (EAS)

AF:

0.961

AC:

4978

AN:

5182

South Asian (SAS)

AF:

0.713

AC:

3433

AN:

4816

European-Finnish (FIN)

AF:

0.899

AC:

9521

AN:

10596

Middle Eastern (MID)

AF:

0.656

AC:

193

AN:

294

European-Non Finnish (NFE)

AF:

0.854

AC:

58065

AN:

68002

Other (OTH)

AF:

0.771

AC:

1627

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1242

2483

3725

4966

6208

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

834

1668

2502

3336

4170

<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:

0.785

Hom.:

15144

Bravo

AF:

0.732

Asia WGS

AF:

0.823

AC:

2863

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jan 30, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Psychomotor retardation, epilepsy, and craniofacial dysmorphism

Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

7.9

(source)

DANN

Benign

0.49

PhyloP100

0.79

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000080

dbscSNV1_RF

Benign

0.0080

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over