1-15875007-G-T

Variant names:

• chr1-15875007-G-T
• rs16852052
• NM_015001.3:c.405-1195G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015001.3(SPEN):​c.405-1195G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0979 in 152,054 control chromosomes in the GnomAD database, including 968 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 0.098 (968 hom., cov: 32)
• Consequence: SPEN NM_015001.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.148
• Publications: 8 publications found

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]

SPEN Gene-Disease associations (from GenCC):

• Radio-Tartaglia syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, G2P, ClinGen, Labcorp Genetics (formerly Invitae)
• complex neurodevelopmental disorder

  Inheritance: AD Classification: NO_KNOWN Submitted by: Illumina

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015001.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPEN	NM_015001.3	MANE Select	c.405-1195G>T		intron	N/A	NP_055816.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPEN	ENST00000375759.8	TSL:1 MANE Select	c.405-1195G>T		intron	N/A	ENSP00000364912.3	Q96T58
	SPEN	ENST00000673875.1		c.201-1195G>T		intron	N/A	ENSP00000501122.1	A0A669KB49
	SPEN	ENST00000438066.2	TSL:3	n.*1255+612G>T		intron	N/A	ENSP00000388021.2	F6WRY4

Frequencies

GnomAD3 genomes AF: 0.0979 AC: 14881 AN: 151932 Hom.: 970 Cov.: 32

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.0615

Gnomad AMR AF: 0.0540

Gnomad ASJ AF: 0.104

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0286

Gnomad FIN AF: 0.0924

Gnomad MID AF: 0.0541

Gnomad NFE AF: 0.0748

Gnomad OTH AF: 0.0578

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

GnomAD4 genome AF: 0.0979 AC: 14890 AN: 152054 Hom.: 968 Cov.: 32 AF XY: 0.0964 AC XY: 7165 AN XY: 74340

African (AFR) AF: 0.176 AC: 7316 AN: 41452

American (AMR) AF: 0.0540 AC: 824 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.104 AC: 362 AN: 3470

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5184

South Asian (SAS) AF: 0.0280 AC: 135 AN: 4824

European-Finnish (FIN) AF: 0.0924 AC: 977 AN: 10572

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0748 AC: 5083 AN: 67964

Other (OTH) AF: 0.0567 AC: 120 AN: 2116

Alfa AF: 0.0810 Hom.: 2022

Bravo AF: 0.0990

Asia WGS AF: 0.0200 AC: 70 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.2
DANN	Benign	0.63
PhyloP100		-0.15
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs16852052; hg19: chr1-16201502;