16-85634339-C-G

Position:

• chr16-85634339-C-G

Variant summary

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

The NM_014615.5(GSE1):​c.226+207C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.565 in 152,186 control chromosomes in the GnomAD database, including 24,975 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 0.57 (24975 hom., cov: 35)
• Consequence: GSE1 NM_014615.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.542

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 = 0.636 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GSE1	NM_014615.5	c.226+207C>G		intron_variant		ENST00000253458.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSE1	ENST00000253458.12	c.226+207C>G		intron_variant		5	NM_014615.5	A2

Frequencies

GnomAD3 genomes AF: 0.565 AC: 85931 AN: 152068 Hom.: 24965 Cov.: 35

Gnomad AFR AF: 0.445

Gnomad AMI AF: 0.521

Gnomad AMR AF: 0.570

Gnomad ASJ AF: 0.627

Gnomad EAS AF: 0.402

Gnomad SAS AF: 0.518

Gnomad FIN AF: 0.618

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.642

Gnomad OTH AF: 0.580

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

GnomAD4 genome AF: 0.565 AC: 85987 AN: 152186 Hom.: 24975 Cov.: 35 AF XY: 0.562 AC XY: 41833 AN XY: 74404

Gnomad4 AFR AF: 0.445

Gnomad4 AMR AF: 0.570

Gnomad4 ASJ AF: 0.627

Gnomad4 EAS AF: 0.402

Gnomad4 SAS AF: 0.519

Gnomad4 FIN AF: 0.618

Gnomad4 NFE AF: 0.642

Gnomad4 OTH AF: 0.575

Alfa AF: 0.601 Hom.: 3392

Bravo AF: 0.555

Asia WGS AF: 0.475 AC: 1653 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	1.9
DANN	Benign	0.61
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs7405052; hg19: chr16-85667945;