rs4783187

Positions:

• chr16-85382232-T-C

Variant summary

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

The ENST00000637419.1(GSE1):​c.2464+24589T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.833 in 152,218 control chromosomes in the GnomAD database, including 53,014 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 0.83 (53014 hom., cov: 33)
• Consequence: GSE1 ENST00000637419.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.660

Genes affected

GSE1 (HGNC:28979): (Gse1 coiled-coil protein) This gene encodes a proline-rich protein with coiled coil domains that may be a subunit of a BRAF35-HDAC (BHC) histone deacetylase complex. This gene may function as an oncogene in breast cancer and enhanced expression of the encoded protein has been observed in breast cancer patients. [provided by RefSeq, May 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.869 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GSE1	XM_005255859.6	c.2131+24589T>C		intron_variant			XP_005255916.3
GSE1	XM_005255860.4	c.2131+24589T>C		intron_variant			XP_005255917.3
GSE1	XM_005255861.6	c.2131+24589T>C		intron_variant			XP_005255918.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GSE1	ENST00000637419.1	c.2464+24589T>C		intron_variant		5		ENSP00000490157.1

Frequencies

GnomAD3 genomes AF: 0.833 AC: 126729 AN: 152100 Hom.: 52969 Cov.: 33

Gnomad AFR AF: 0.781

Gnomad AMI AF: 0.818

Gnomad AMR AF: 0.783

Gnomad ASJ AF: 0.892

Gnomad EAS AF: 0.825

Gnomad SAS AF: 0.796

Gnomad FIN AF: 0.843

Gnomad MID AF: 0.867

Gnomad NFE AF: 0.875

Gnomad OTH AF: 0.853

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

GnomAD4 genome AF: 0.833 AC: 126827 AN: 152218 Hom.: 53014 Cov.: 33 AF XY: 0.830 AC XY: 61746 AN XY: 74432

Gnomad4 AFR AF: 0.781

Gnomad4 AMR AF: 0.782

Gnomad4 ASJ AF: 0.892

Gnomad4 EAS AF: 0.825

Gnomad4 SAS AF: 0.795

Gnomad4 FIN AF: 0.843

Gnomad4 NFE AF: 0.875

Gnomad4 OTH AF: 0.856

Alfa AF: 0.866 Hom.: 115319

Bravo AF: 0.826

Asia WGS AF: 0.789 AC: 2747 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.9
DANN	Benign	0.54

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4783187; hg19: chr16-85415838;