rs2174769

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_024700.4(SNIP1):c.328-3T>C variant causes a splice region, splice polypyrimidine tract, 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, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00007978

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.792

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 1167876.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-37540758-A-G is described in Lovd as [Benign].

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/exons	MANE	UniProt
SNIP1	NM_024700.4 linkuse as main transcript	c.328-3T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000296215.8

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris
SNIP1	ENST00000296215.8 linkuse as main transcript	c.328-3T>C	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_024700.4	P1
SNIP1	ENST00000638725.1 linkuse as main transcript	n.837T>C	non_coding_transcript_exon_variant	1/2	2
SNIP1	ENST00000468040.2 linkuse as main transcript	c.*102-3T>C	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant		5

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

GnomAD3 exomes

AF:

0.820

AC:

191782

AN:

233950

Hom.:

80345

AF XY:

0.818

AC XY:

103961

AN XY:

127088

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 SAS exome

AF:

0.718

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

Gnomad4 AFR exome

AF:

0.454

Gnomad4 AMR exome

AF:

0.878

Gnomad4 ASJ exome

AF:

0.768

Gnomad4 EAS exome

AF:

0.954

Gnomad4 SAS exome

AF:

0.719

Gnomad4 FIN exome

AF:

0.892

Gnomad4 NFE exome

AF:

0.861

Gnomad4 OTH exome

AF:

0.820

GnomAD4 genome

AF:

0.747

AC:

113562

AN:

152118

Hom.:

44743

Cov.:

AF XY:

0.749

AC XY:

55723

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.475

Gnomad4 AMR

AF:

0.835

Gnomad4 ASJ

AF:

0.755

Gnomad4 EAS

AF:

0.961

Gnomad4 SAS

AF:

0.713

Gnomad4 FIN

AF:

0.899

Gnomad4 NFE

AF:

0.854

Gnomad4 OTH

AF:

0.771

Alfa

AF:

0.802

Hom.:

13957

Bravo

AF:

0.732

Asia WGS

AF:

0.823

AC:

2863

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 30, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -

Psychomotor retardation, epilepsy, and craniofacial dysmorphism

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

Cadd

Benign

7.9

Dann

Benign

0.49

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over