1-15875007-G-T

Position:

• chr1-15875007-G-T

Variant summary

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

The ENST00000375759.8(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 ENST00000375759.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.148

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPEN	NM_015001.3	c.405-1195G>T		intron_variant		ENST00000375759.8	NP_055816.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPEN	ENST00000375759.8	c.405-1195G>T		intron_variant		1	NM_015001.3	ENSP00000364912	P1
SPEN	ENST00000673875.1	c.201-1195G>T		intron_variant				ENSP00000501122
SPEN	ENST00000438066.2	c.*1255+612G>T		intron_variant, NMD_transcript_variant		3		ENSP00000388021
SPEN	ENST00000471538.1	n.894+612G>T		intron_variant, non_coding_transcript_variant		2

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

Gnomad4 AFR AF: 0.176

Gnomad4 AMR AF: 0.0540

Gnomad4 ASJ AF: 0.104

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0280

Gnomad4 FIN AF: 0.0924

Gnomad4 NFE AF: 0.0748

Gnomad4 OTH AF: 0.0567

Alfa AF: 0.0738 Hom.: 994

Bravo AF: 0.0990

Asia WGS AF: 0.0200 AC: 70 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.2
DANN	Benign	0.63

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: rs16852052; hg19: chr1-16201502;