1-15872825-C-T

Variant names:

• chr1-15872825-C-T
• rs150922162
• NM_015001.3:c.93C>T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BS1 BS2

The NM_015001.3(SPEN):​c.93C>T​(p.Arg31Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00367 in 1,492,066 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0016 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0039 (15 hom.)
• Consequence: SPEN NM_015001.3 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -2.16

Genes affected

SPEN (HGNC:17575): (spen family transcriptional repressor) This gene encodes a hormone inducible transcriptional repressor. Repression of transcription by this gene product can occur through interactions with other repressors, by the recruitment of proteins involved in histone deacetylation, or through sequestration of transcriptional activators. The product of this gene contains a carboxy-terminal domain that permits binding to other corepressor proteins. This domain also permits interaction with members of the NuRD complex, a nucleosome remodeling protein complex that contains deacetylase activity. In addition, this repressor contains several RNA recognition motifs that confer binding to a steroid receptor RNA coactivator; this binding can modulate the activity of both liganded and nonliganded steroid receptors. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP6: Variant 1-15872825-C-T is Benign according to our data. Variant chr1-15872825-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3038799.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-2.16 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00163 (248/152186) while in subpopulation NFE AF= 0.00273 (186/68014). AF 95% confidence interval is 0.00241. There are 1 homozygotes in gnomad4. There are 108 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 248 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPEN	NM_015001.3	c.93C>T	p.Arg31Arg	synonymous_variant	Exon 2 of 15	ENST00000375759.8	NP_055816.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPEN	ENST00000375759.8	c.93C>T	p.Arg31Arg	synonymous_variant	Exon 2 of 15	1	NM_015001.3	ENSP00000364912.3
SPEN	ENST00000673875	c.-112C>T		5_prime_UTR_variant	Exon 3 of 12			ENSP00000501122.1
SPEN	ENST00000438066.2	n.93C>T		non_coding_transcript_exon_variant	Exon 2 of 15	3		ENSP00000388021.2

Frequencies

GnomAD3 genomes AF: 0.00163 AC: 248 AN: 152070 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000676

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00157

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00273

Gnomad OTH AF: 0.00192

GnomAD3 exomes AF: 0.00148 AC: 283 AN: 191196 Hom.: 0 AF XY: 0.00160 AC XY: 163 AN XY: 101804

Gnomad AFR exome AF: 0.000778

Gnomad AMR exome AF: 0.000895

Gnomad ASJ exome AF: 0.000649

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000562

Gnomad FIN exome AF: 0.000168

Gnomad NFE exome AF: 0.00253

Gnomad OTH exome AF: 0.00229

GnomAD4 exome AF: 0.00391 AC: 5233 AN: 1339880 Hom.: 15 Cov.: 31 AF XY: 0.00379 AC XY: 2481 AN XY: 654330

Gnomad4 AFR exome AF: 0.000660

Gnomad4 AMR exome AF: 0.00107

Gnomad4 ASJ exome AF: 0.000651

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000153

Gnomad4 FIN exome AF: 0.000183

Gnomad4 NFE exome AF: 0.00474

Gnomad4 OTH exome AF: 0.00359

GnomAD4 genome AF: 0.00163 AC: 248 AN: 152186 Hom.: 1 Cov.: 32 AF XY: 0.00145 AC XY: 108 AN XY: 74382

Gnomad4 AFR AF: 0.000674

Gnomad4 AMR AF: 0.00157

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000189

Gnomad4 NFE AF: 0.00273

Gnomad4 OTH AF: 0.00190

Alfa AF: 0.00201 Hom.: 1

Bravo AF: 0.00180

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

SPEN-related disorder Benign:1

Apr 11, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	0.57
DANN	Benign	0.53
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8

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: rs150922162; hg19: chr1-16199320; COSMIC: COSV65364696; COSMIC: COSV65364696;