16-85591521-G-T

Variant names:

• chr16-85591521-G-T
• rs4240810
• ENST00000637419.1:c.2465-42393G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000637419.1(GSE1):​c.2465-42393G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.67 in 152,156 control chromosomes in the GnomAD database, including 34,604 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 0.67 (34604 hom., cov: 34)
• Consequence: GSE1 ENST00000637419.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.199
• Publications: 4 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.875 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSE1	XM_005255859.6	c.2132-42393G>T		intron_variant	Intron 2 of 16		XP_005255916.3
GSE1	XM_005255860.4	c.2132-42393G>T		intron_variant	Intron 2 of 15		XP_005255917.3
GSE1	XM_005255861.6	c.2132-57031G>T		intron_variant	Intron 2 of 15		XP_005255918.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSE1	ENST00000637419.1	c.2465-42393G>T		intron_variant	Intron 2 of 2	5		ENSP00000490157.1
GSE1	ENST00000635906.1	c.37+35158G>T		intron_variant	Intron 1 of 2	3		ENSP00000490289.1

Frequencies

GnomAD3 genomes AF: 0.670 AC: 101895 AN: 152038 Hom.: 34584 Cov.: 34

Gnomad AFR AF: 0.567

Gnomad AMI AF: 0.608

Gnomad AMR AF: 0.760

Gnomad ASJ AF: 0.640

Gnomad EAS AF: 0.897

Gnomad SAS AF: 0.698

Gnomad FIN AF: 0.679

Gnomad MID AF: 0.669

Gnomad NFE AF: 0.694

Gnomad OTH AF: 0.670

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

GnomAD4 genome AF: 0.670 AC: 101960 AN: 152156 Hom.: 34604 Cov.: 34 AF XY: 0.674 AC XY: 50132 AN XY: 74368

African (AFR) AF: 0.567 AC: 23546 AN: 41500

American (AMR) AF: 0.760 AC: 11638 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.640 AC: 2218 AN: 3468

East Asian (EAS) AF: 0.896 AC: 4631 AN: 5166

South Asian (SAS) AF: 0.698 AC: 3366 AN: 4824

European-Finnish (FIN) AF: 0.679 AC: 7182 AN: 10582

Middle Eastern (MID) AF: 0.682 AC: 199 AN: 292

European-Non Finnish (NFE) AF: 0.694 AC: 47215 AN: 67996

Other (OTH) AF: 0.668 AC: 1413 AN: 2116

Alfa AF: 0.691 Hom.: 100304

Bravo AF: 0.675

Asia WGS AF: 0.755 AC: 2625 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.0
DANN	Benign	0.87
PhyloP100		-0.20

Splicing

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

Other links and lift over

dbSNP: rs4240810; hg19: chr16-85625127;