rs142740888

Variant names:

• chr7-127701159-C-T
• rs142740888
• NM_014390.4:c.429-4C>T

Variant summary

Our verdict is Benign. The variant received -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, 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, intron
• Scores: Splicing: ADA: 0.001688
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.710
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -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 GnomAd4 at 289 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SND1	NM_014390.4	c.429-4C>T		splice_region_variant, intron_variant	Intron 4 of 23	ENST00000354725.8	NP_055205.2
SND1	XM_017011987.3	c.429-4C>T		splice_region_variant, intron_variant	Intron 4 of 16		XP_016867476.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SND1	ENST00000354725.8	c.429-4C>T		splice_region_variant, intron_variant	Intron 4 of 23	1	NM_014390.4	ENSP00000346762.3
SND1	ENST00000468621.5	n.444-4C>T		splice_region_variant, intron_variant	Intron 4 of 4	4
SND1	ENST00000483503.5	n.324-4C>T		splice_region_variant, intron_variant	Intron 3 of 5	5
SND1	ENST00000492772.1	n.236-4C>T		splice_region_variant, intron_variant	Intron 3 of 5	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

GnomAD2 exomes AF: 0.00243 AC: 609 AN: 250800 AF XY: 0.00255

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 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

African (AFR) AF: 0.000359 AC: 12 AN: 33436

American (AMR) AF: 0.000202 AC: 9 AN: 44652

Ashkenazi Jewish (ASJ) AF: 0.0111 AC: 289 AN: 26104

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39686

South Asian (SAS) AF: 0.00244 AC: 210 AN: 86142

European-Finnish (FIN) AF: 0.00290 AC: 155 AN: 53402

Middle Eastern (MID) AF: 0.000868 AC: 5 AN: 5760

European-Non Finnish (NFE) AF: 0.00271 AC: 3014 AN: 1111680

Other (OTH) AF: 0.00240 AC: 145 AN: 60358

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

African (AFR) AF: 0.000362 AC: 15 AN: 41464

American (AMR) AF: 0.000262 AC: 4 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00865 AC: 30 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5172

South Asian (SAS) AF: 0.00166 AC: 8 AN: 4820

European-Finnish (FIN) AF: 0.00228 AC: 24 AN: 10546

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00297 AC: 202 AN: 67984

Other (OTH) AF: 0.00237 AC: 5 AN: 2112

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

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	9.9
DANN	Benign	0.82
PhyloP100		0.71
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs142740888; hg19: chr7-127341213;