16-85635770-C-T

Variant names:

• chr16-85635770-C-T
• rs8045380
• NM_014615.5:c.226+1638C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014615.5. 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
	GSE1	NM_014615.5	MANE Select	c.226+1638C>T		intron	N/A	NP_055430.1	Q14687-1
	GSE1	NM_001278184.3		c.8-12782C>T		intron	N/A	NP_001265113.1	Q14687-3
	GSE1	NM_001134473.3		c.-86-12782C>T		intron	N/A	NP_001127945.1	Q14687-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSE1	ENST00000253458.12	TSL:5 MANE Select	c.226+1638C>T		intron	N/A	ENSP00000253458.6	Q14687-1
	GSE1	ENST00000393243.5	TSL:1	c.8-12782C>T		intron	N/A	ENSP00000376934.1	Q14687-3
	GSE1	ENST00000405402.6	TSL:1	c.-86-12782C>T		intron	N/A	ENSP00000384839.2	Q14687-2

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

African (AFR) AF: 0.305 AC: 12640 AN: 41502

American (AMR) AF: 0.205 AC: 3140 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.278 AC: 964 AN: 3466

East Asian (EAS) AF: 0.00328 AC: 17 AN: 5188

South Asian (SAS) AF: 0.166 AC: 804 AN: 4830

European-Finnish (FIN) AF: 0.255 AC: 2697 AN: 10596

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.296 AC: 20084 AN: 67964

Other (OTH) AF: 0.241 AC: 508 AN: 2112

Alfa AF: 0.272 Hom.: 6878

Bravo AF: 0.268

Asia WGS AF: 0.0830 AC: 290 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.1
DANN	Benign	0.87
PhyloP100		0.036
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: rs8045380; hg19: chr16-85669376;