rs2023902

Positions:

• chr11-17852679-A-C

Variant summary

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

The NM_012139.4(SERGEF):​c.1048+25529T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 152,272 control chromosomes in the GnomAD database, including 2,341 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 0.16 (2341 hom., cov: 32)
• Consequence: SERGEF NM_012139.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.24

Genes affected

SERGEF (HGNC:17499): (secretion regulating guanine nucleotide exchange factor) Predicted to enable guanyl-nucleotide exchange factor activity. Involved in negative regulation of protein secretion. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

KCNC1 (HGNC:6233): (potassium voltage-gated channel subfamily C member 1) This gene encodes a member of a family of integral membrane proteins that mediate the voltage-dependent potassium ion permeability of excitable membranes. Alternative splicing is thought to result in two transcript variants encoding isoforms that differ at their C-termini. These isoforms have had conflicting names in the literature: the longer isoform has been called both "b" and "alpha", while the shorter isoform has been called both "a" and "beta" (PMIDs 1432046, 12091563). [provided by RefSeq, Oct 2014]

LOC107984317 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SERGEF	NM_012139.4	c.1048+25529T>G		intron_variant		ENST00000265965.10	NP_036271.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SERGEF	ENST00000265965.10	c.1048+25529T>G		intron_variant		1	NM_012139.4	ENSP00000265965.5

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25033 AN: 152152 Hom.: 2343 Cov.: 32

Gnomad AFR AF: 0.0861

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.283

Gnomad EAS AF: 0.111

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.172

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.212

Gnomad OTH AF: 0.187

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

GnomAD4 genome AF: 0.164 AC: 25024 AN: 152272 Hom.: 2341 Cov.: 32 AF XY: 0.163 AC XY: 12124 AN XY: 74456

Gnomad4 AFR AF: 0.0860

Gnomad4 AMR AF: 0.141

Gnomad4 ASJ AF: 0.283

Gnomad4 EAS AF: 0.111

Gnomad4 SAS AF: 0.190

Gnomad4 FIN AF: 0.172

Gnomad4 NFE AF: 0.212

Gnomad4 OTH AF: 0.185

Alfa AF: 0.201 Hom.: 1618

Bravo AF: 0.157

Asia WGS AF: 0.152 AC: 530 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	9.7
DANN	Benign	0.71

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: rs2023902; hg19: chr11-17874226;