rs12672945

Positions:

• chr7-127870436-A-G
• chr7-127870436-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014390.4(SND1):​c.1344-17466A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 152,026 control chromosomes in the GnomAD database, including 6,263 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.25 (6263 hom., cov: 32)
• Consequence: SND1 NM_014390.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.504

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.651 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SND1	NM_014390.4	c.1344-17466A>G		intron_variant		ENST00000354725.8	NP_055205.2
SND1	XM_017011987.3	c.1344-17466A>G		intron_variant			XP_016867476.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SND1	ENST00000354725.8	c.1344-17466A>G		intron_variant		1	NM_014390.4	ENSP00000346762	P1
SND1	ENST00000465900.5	n.407-17466A>G		intron_variant, non_coding_transcript_variant		4
SND1	ENST00000468166.5	n.505-17466A>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38243 AN: 151908 Hom.: 6259 Cov.: 32

Gnomad AFR AF: 0.0611

Gnomad AMI AF: 0.220

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.669

Gnomad SAS AF: 0.374

Gnomad FIN AF: 0.369

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.259

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.252 AC: 38250 AN: 152026 Hom.: 6263 Cov.: 32 AF XY: 0.260 AC XY: 19345 AN XY: 74292

Gnomad4 AFR AF: 0.0609

Gnomad4 AMR AF: 0.269

Gnomad4 ASJ AF: 0.195

Gnomad4 EAS AF: 0.669

Gnomad4 SAS AF: 0.376

Gnomad4 FIN AF: 0.369

Gnomad4 NFE AF: 0.309

Gnomad4 OTH AF: 0.259

Alfa AF: 0.272 Hom.: 1029

Bravo AF: 0.235

Asia WGS AF: 0.464 AC: 1610 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.5
DANN	Benign	0.70

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs12672945; hg19: chr7-127510489; COSMIC: COSV61238616;