11-17902217-T-C

Variant names:

• chr11-17902217-T-C
• rs549485
• NM_012139.4:c.1012-23973A>G

Variant summary

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

The NM_012139.4(SERGEF):​c.1012-23973A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.671 in 151,972 control chromosomes in the GnomAD database, including 34,978 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 0.67 (34978 hom., cov: 31)
• Consequence: SERGEF NM_012139.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.769 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.1012-23973A>G		intron	N/A	NP_036271.1
	SERGEF	NR_104040.2		n.1133+16478A>G		intron	N/A
	SERGEF	NR_104041.2		n.882-23973A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERGEF	ENST00000265965.10	TSL:1 MANE Select	c.1012-23973A>G		intron	N/A	ENSP00000265965.5
	SERGEF	ENST00000528200.5	TSL:1	c.845-23973A>G		intron	N/A	ENSP00000434188.1
	SERGEF	ENST00000525422.5	TSL:1	n.*31+16478A>G		intron	N/A	ENSP00000434330.1

Frequencies

GnomAD3 genomes AF: 0.671 AC: 101826 AN: 151856 Hom.: 34950 Cov.: 31

Gnomad AFR AF: 0.776

Gnomad AMI AF: 0.619

Gnomad AMR AF: 0.568

Gnomad ASJ AF: 0.558

Gnomad EAS AF: 0.282

Gnomad SAS AF: 0.641

Gnomad FIN AF: 0.690

Gnomad MID AF: 0.623

Gnomad NFE AF: 0.666

Gnomad OTH AF: 0.640

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

GnomAD4 genome AF: 0.671 AC: 101907 AN: 151972 Hom.: 34978 Cov.: 31 AF XY: 0.666 AC XY: 49455 AN XY: 74286

African (AFR) AF: 0.776 AC: 32164 AN: 41446

American (AMR) AF: 0.567 AC: 8655 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.558 AC: 1933 AN: 3466

East Asian (EAS) AF: 0.283 AC: 1459 AN: 5162

South Asian (SAS) AF: 0.640 AC: 3084 AN: 4818

European-Finnish (FIN) AF: 0.690 AC: 7280 AN: 10544

Middle Eastern (MID) AF: 0.616 AC: 181 AN: 294

European-Non Finnish (NFE) AF: 0.666 AC: 45230 AN: 67962

Other (OTH) AF: 0.642 AC: 1358 AN: 2114

Alfa AF: 0.638 Hom.: 15239

Bravo AF: 0.663

Asia WGS AF: 0.520 AC: 1808 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.29
DANN	Benign	0.29
PhyloP100		-1.1
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: rs549485; hg19: chr11-17923764;