Variant chr1-15874303-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBS1BS2

The NM_015001.3(SPEN):c.404+1167C>T variant causes a intron change. The variant allele was found at a frequency of 0.000476 in 1,366,436 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00036 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00049 ( 5 hom. )

Consequence

SPEN
NM_015001.3 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.70

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.32).

BP6

Variant 1-15874303-C-T is Benign according to our data. Variant chr1-15874303-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2638299.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000361 (55/152208) while in subpopulation SAS AF= 0.00249 (12/4824). AF 95% confidence interval is 0.00144. There are 0 homozygotes in gnomad4. There are 31 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 55 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPEN	NM_015001.3 linkuse as main transcript	c.404+1167C>T		intron_variant		ENST00000375759.8	NP_055816.2

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris
SPEN	ENST00000375759.8 linkuse as main transcript	c.404+1167C>T	intron_variant		1	NM_015001.3	ENSP00000364912	P1
SPEN	ENST00000673875.1 linkuse as main transcript	c.200+1167C>T	intron_variant				ENSP00000501122
SPEN	ENST00000471538.1 linkuse as main transcript	n.802C>T	non_coding_transcript_exon_variant	1/2	2
SPEN	ENST00000438066.2 linkuse as main transcript	c.*1163C>T	3_prime_UTR_variant, NMD_transcript_variant	2/15	3		ENSP00000388021

Frequencies

GnomAD3 genomes

AF:

0.000362

AC:

AN:

152090

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000459

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00249

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000441

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000758

AC:

183

AN:

241424

Hom.:

AF XY:

0.000950

AC XY:

126

AN XY:

132574

show subpopulations

Gnomad AFR exome

AF:

0.000210

Gnomad AMR exome

AF:

0.000494

Gnomad ASJ exome

AF:

0.000605

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00306

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000560

Gnomad OTH exome

AF:

0.000670

GnomAD4 exome

AF:

0.000490

AC:

595

AN:

1214228

Hom.:

Cov.:

AF XY:

0.000635

AC XY:

382

AN XY:

601764

show subpopulations

Gnomad4 AFR exome

AF:

0.0000761

Gnomad4 AMR exome

AF:

0.000402

Gnomad4 ASJ exome

AF:

0.000474

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00303

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000297

Gnomad4 OTH exome

AF:

0.000591

GnomAD4 genome

AF:

0.000361

AC:

AN:

152208

Hom.:

Cov.:

AF XY:

0.000417

AC XY:

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.000459

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00249

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000441

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.000565

Hom.:

Bravo

AF:

0.000359

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.000818

EpiControl

AF:

0.000889

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

SPEN: BS1 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Benign

0.67

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over