16-85635770-C-T

Variant summary

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

The NM_014615.5(GSE1):c.226+1638C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 152,158 control chromosomes in the GnomAD database, including 5,960 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 0.27 (5960 hom., cov: 34)
• Consequence: GSE1 NM_014615.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0360

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.3 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GSE1	NM_014615.5	c.226+1638C>T		intron_variant		ENST00000253458.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSE1	ENST00000253458.12	c.226+1638C>T		intron_variant		5	NM_014615.5	A2

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41195 AN: 152040 Hom.: 5958 Cov.: 34

Gnomad AFR AF: 0.305

Gnomad AMI AF: 0.296

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.278

Gnomad EAS AF: 0.00327

Gnomad SAS AF: 0.168

Gnomad FIN AF: 0.255

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.296

Gnomad OTH AF: 0.244

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

GnomAD4 genome AF: 0.271 AC: 41200 AN: 152158 Hom.: 5960 Cov.: 34 AF XY: 0.263 AC XY: 19592 AN XY: 74388

Gnomad4 AFR AF: 0.305

Gnomad4 AMR AF: 0.205

Gnomad4 ASJ AF: 0.278

Gnomad4 EAS AF: 0.00328

Gnomad4 SAS AF: 0.166

Gnomad4 FIN AF: 0.255

Gnomad4 NFE AF: 0.296

Gnomad4 OTH AF: 0.241

Alfa AF: 0.277 Hom.: 2362

Bravo AF: 0.268

Asia WGS AF: 0.0830 AC: 290 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	4.1
Dann	Benign	0.87

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: rs8045380; hg19: chr16-85669376;