rs11024433

Variant names:

• chr11-17922578-G-A
• rs11024433
• NM_012139.4:c.1011+36892C>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.1011+36892C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 152,024 control chromosomes in the GnomAD database, including 3,639 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 0.19 (3639 hom., cov: 32)
• Consequence: SERGEF NM_012139.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0730
• Publications: 6 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.27 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.1011+36892C>T		intron	N/A	NP_036271.1	Q9UGK8-1
	SERGEF	NR_104040.2		n.1049-3799C>T		intron	N/A
	SERGEF	NR_104041.2		n.882-44334C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERGEF	ENST00000265965.10	TSL:1 MANE Select	c.1011+36892C>T		intron	N/A	ENSP00000265965.5	Q9UGK8-1
	SERGEF	ENST00000528200.5	TSL:1	c.845-44334C>T		intron	N/A	ENSP00000434188.1	Q9UGK8-2
	SERGEF	ENST00000525422.5	TSL:1	n.1012-3799C>T		intron	N/A	ENSP00000434330.1	G3V1B4

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29263 AN: 151906 Hom.: 3637 Cov.: 32

Gnomad AFR AF: 0.0561

Gnomad AMI AF: 0.347

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.204

Gnomad EAS AF: 0.0349

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.302

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.273

Gnomad OTH AF: 0.210

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

GnomAD4 genome AF: 0.193 AC: 29265 AN: 152024 Hom.: 3639 Cov.: 32 AF XY: 0.193 AC XY: 14304 AN XY: 74300

African (AFR) AF: 0.0559 AC: 2319 AN: 41476

American (AMR) AF: 0.179 AC: 2728 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.204 AC: 706 AN: 3466

East Asian (EAS) AF: 0.0352 AC: 182 AN: 5172

South Asian (SAS) AF: 0.159 AC: 765 AN: 4824

European-Finnish (FIN) AF: 0.302 AC: 3180 AN: 10530

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.273 AC: 18569 AN: 67978

Other (OTH) AF: 0.209 AC: 440 AN: 2110

Alfa AF: 0.240 Hom.: 2570

Bravo AF: 0.180

Asia WGS AF: 0.0980 AC: 343 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.0
DANN	Benign	0.59
PhyloP100		0.073
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: rs11024433; hg19: chr11-17944125;