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. Variant got -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

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]

ACMG classification

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 rank	MANE	Protein	UniProt
SNIP1	NM_024700.4	c.328-3T>C		splice_region_variant, intron_variant	Intron 2 of 3	ENST00000296215.8	NP_078976.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNIP1	ENST00000296215.8	c.328-3T>C		splice_region_variant, intron_variant	Intron 2 of 3	1	NM_024700.4	ENSP00000296215.5
SNIP1	ENST00000638725.1	n.837T>C		non_coding_transcript_exon_variant	Exon 1 of 2	2
SNIP1	ENST00000468040.2	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.: 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

GnomAD3 exomes AF: 0.820 AC: 191782 AN: 233950 Hom.: 80345 AF XY: 0.818 AC XY: 103961 AN XY: 127088

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

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.: 32 AF XY: 0.749 AC XY: 55723 AN XY: 74380

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:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

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

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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
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

Other links and lift over

dbSNP: rs2174769; hg19: chr1-38006359;