rs493767

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SERGEF	NM_012139.4	c.1012-8050G>C		intron_variant		ENST00000265965.10	NP_036271.1
SERGEF	NR_104040.2	n.1134-8050G>C		intron_variant
SERGEF	NR_104041.2	n.882-8050G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SERGEF	ENST00000265965.10	c.1012-8050G>C		intron_variant		1	NM_012139.4	ENSP00000265965.5

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

Gnomad4 AFR AF: 0.550

Gnomad4 AMR AF: 0.535

Gnomad4 ASJ AF: 0.552

Gnomad4 EAS AF: 0.489

Gnomad4 SAS AF: 0.640

Gnomad4 FIN AF: 0.690

Gnomad4 NFE AF: 0.661

Gnomad4 OTH AF: 0.620

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	6.9
DANN	Benign	0.91

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: rs493767; hg19: chr11-17907841;