rs493767

Variant names:

• chr11-17886294-C-G
• rs493767
• NM_012139.4:c.1012-8050G>C

Your query was ambiguous. Multiple possible variants found:

• chr11-17886294-C-G
• chr11-17886294-C-T

Variant summary

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

The NM_012139.4(SERGEF):​c.1012-8050G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.61 in 151,950 control chromosomes in the GnomAD database, including 28,647 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 0.61 (28647 hom., cov: 31)
• Consequence: SERGEF NM_012139.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.134
• Publications: 1 publications found

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]

ENSG00000302476 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.656 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012139.4. 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
	SERGEF	NM_012139.4	MANE Select	c.1012-8050G>C		intron	N/A	NP_036271.1	Q9UGK8-1
	SERGEF	NR_104040.2		n.1134-8050G>C		intron	N/A
	SERGEF	NR_104041.2		n.882-8050G>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERGEF	ENST00000265965.10	TSL:1 MANE Select	c.1012-8050G>C		intron	N/A	ENSP00000265965.5	Q9UGK8-1
	SERGEF	ENST00000528200.5	TSL:1	c.845-8050G>C		intron	N/A	ENSP00000434188.1	Q9UGK8-2
	SERGEF	ENST00000525422.5	TSL:1	n.*32-8050G>C		intron	N/A	ENSP00000434330.1	G3V1B4

Frequencies

GnomAD3 genomes AF: 0.611 AC: 92694 AN: 151832 Hom.: 28634 Cov.: 31

Gnomad AFR AF: 0.550

Gnomad AMI AF: 0.619

Gnomad AMR AF: 0.535

Gnomad ASJ AF: 0.552

Gnomad EAS AF: 0.490

Gnomad SAS AF: 0.642

Gnomad FIN AF: 0.690

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.662

Gnomad OTH AF: 0.616

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

GnomAD4 genome AF: 0.610 AC: 92746 AN: 151950 Hom.: 28647 Cov.: 31 AF XY: 0.609 AC XY: 45269 AN XY: 74280

African (AFR) AF: 0.550 AC: 22758 AN: 41386

American (AMR) AF: 0.535 AC: 8161 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.552 AC: 1916 AN: 3470

East Asian (EAS) AF: 0.489 AC: 2522 AN: 5160

South Asian (SAS) AF: 0.640 AC: 3078 AN: 4806

European-Finnish (FIN) AF: 0.690 AC: 7299 AN: 10574

Middle Eastern (MID) AF: 0.602 AC: 177 AN: 294

European-Non Finnish (NFE) AF: 0.661 AC: 44962 AN: 67972

Other (OTH) AF: 0.620 AC: 1311 AN: 2114

Alfa AF: 0.633 Hom.: 3848

Bravo AF: 0.594

Asia WGS AF: 0.610 AC: 2120 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	6.9
DANN	Benign	0.91
PhyloP100		-0.13
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: rs493767; hg19: chr11-17907841;