7-127701159-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The NM_014390.4(SND1):c.429-4C>T 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 0.00256 in 1,613,262 control chromosomes in the GnomAD database, including 13 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 0.0019 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0026 (11 hom.)
• Consequence: SND1 NM_014390.4 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.001688
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.710

Genes affected

SND1 (HGNC:30646): (staphylococcal nuclease and tudor domain containing 1) This gene encodes a transcriptional co-activator that interacts with the acidic domain of Epstein-Barr virus nuclear antigen 2 (EBNA 2), a transcriptional activator that is required for B-lymphocyte transformation. Other transcription factors that interact with this protein are signal transducers and activators of transcription, STATs. This protein is also thought to be essential for normal cell growth. A similar protein in mammals and other organisms is a component of the RNA-induced silencing complex (RISC). [provided by RefSeq, Jul 2016]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant 7-127701159-C-T is Benign according to our data. Variant chr7-127701159-C-T is described in ClinVar as [Benign]. Clinvar id is 709901.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 289 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SND1	NM_014390.4	c.429-4C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000354725.8
SND1	XM_017011987.3	c.429-4C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SND1	ENST00000354725.8	c.429-4C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_014390.4	P1
SND1	ENST00000468621.5	n.444-4C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		4
SND1	ENST00000483503.5	n.324-4C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		5
SND1	ENST00000492772.1	n.236-4C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.00190 AC: 289 AN: 151924 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000363

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00865

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.00228

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00297

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00243 AC: 609 AN: 250800 Hom.: 2 AF XY: 0.00255 AC XY: 345 AN XY: 135544

Gnomad AFR exome AF: 0.000431

Gnomad AMR exome AF: 0.000203

Gnomad ASJ exome AF: 0.0107

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.00206

Gnomad FIN exome AF: 0.00273

Gnomad NFE exome AF: 0.00305

Gnomad OTH exome AF: 0.00278

GnomAD4 exome AF: 0.00263 AC: 3841 AN: 1461220 Hom.: 11 Cov.: 30 AF XY: 0.00265 AC XY: 1929 AN XY: 726904

Gnomad4 AFR exome AF: 0.000359

Gnomad4 AMR exome AF: 0.000202

Gnomad4 ASJ exome AF: 0.0111

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.00244

Gnomad4 FIN exome AF: 0.00290

Gnomad4 NFE exome AF: 0.00271

Gnomad4 OTH exome AF: 0.00240

GnomAD4 genome AF: 0.00190 AC: 289 AN: 152042 Hom.: 2 Cov.: 32 AF XY: 0.00176 AC XY: 131 AN XY: 74308

Gnomad4 AFR AF: 0.000362

Gnomad4 AMR AF: 0.000262

Gnomad4 ASJ AF: 0.00865

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00166

Gnomad4 FIN AF: 0.00228

Gnomad4 NFE AF: 0.00297

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.00299 Hom.: 0

Bravo AF: 0.00164

Asia WGS AF: 0.00115 AC: 4 AN: 3476

EpiCase AF: 0.00267

EpiControl AF: 0.00202

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
Cadd	Benign	9.9
Dann	Benign	0.82
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0017
dbscSNV1_RF	Benign	0.074
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

LitVar

Other links and lift over

dbSNP: rs142740888; hg19: chr7-127341213;