rs2174769

Variant names:

• chr1-37540758-A-G
• rs2174769
• NM_024700.4:c.328-3T>C

Your query was ambiguous. Multiple possible variants found:

• chr1-37540758-A-G
• chr1-37540758-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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

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: AR, Unknown Classification: MODERATE, LIMITED Submitted by: PanelApp Australia, Illumina, G2P, Labcorp Genetics (formerly Invitae)

ENSG00000307694 (HGNC:):

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024700.4. 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
	SNIP1	NM_024700.4	MANE Select	c.328-3T>C		splice_region intron	N/A	NP_078976.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNIP1	ENST00000296215.8	TSL:1 MANE Select	c.328-3T>C		splice_region intron	N/A	ENSP00000296215.5	Q8TAD8
	SNIP1	ENST00000638725.1	TSL:2	n.837T>C		non_coding_transcript_exon	Exon 1 of 2
	ENSG00000307694	ENST00000827919.1		n.939A>G		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes AF: 0.747 AC: 113480 AN: 152002 Hom.: 44708 Cov.: 32

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

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.: 40 AF XY: 0.840 AC XY: 592217 AN XY: 705402

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

GnomAD4 genome AF: 0.747 AC: 113562 AN: 152118 Hom.: 44743 Cov.: 32 AF XY: 0.749 AC XY: 55723 AN XY: 74380

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

Alfa AF: 0.785 Hom.: 15144

Bravo AF: 0.732

Asia WGS AF: 0.823 AC: 2863 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Psychomotor retardation, epilepsy, and craniofacial dysmorphism (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	7.9
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)

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

Other links and lift over

dbSNP: rs2174769; hg19: chr1-38006359;