11-17904437-G-A

Position:

• chr11-17904437-G-A

Variant summary

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

The NM_012139.4(SERGEF):​c.1012-26193C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.697 in 152,134 control chromosomes in the GnomAD database, including 37,666 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 0.70 (37666 hom., cov: 32)
• Consequence: SERGEF NM_012139.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00500

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.824 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SERGEF	NM_012139.4	c.1012-26193C>T		intron_variant		ENST00000265965.10	NP_036271.1
SERGEF	NR_104040.2	n.1133+14258C>T		intron_variant, non_coding_transcript_variant
SERGEF	NR_104041.2	n.882-26193C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SERGEF	ENST00000265965.10	c.1012-26193C>T		intron_variant		1	NM_012139.4	ENSP00000265965	P1

Frequencies

GnomAD3 genomes AF: 0.697 AC: 105978 AN: 152016 Hom.: 37632 Cov.: 32

Gnomad AFR AF: 0.832

Gnomad AMI AF: 0.610

Gnomad AMR AF: 0.585

Gnomad ASJ AF: 0.559

Gnomad EAS AF: 0.489

Gnomad SAS AF: 0.659

Gnomad FIN AF: 0.705

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.667

Gnomad OTH AF: 0.669

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

GnomAD4 genome AF: 0.697 AC: 106062 AN: 152134 Hom.: 37666 Cov.: 32 AF XY: 0.694 AC XY: 51601 AN XY: 74360

Gnomad4 AFR AF: 0.832

Gnomad4 AMR AF: 0.584

Gnomad4 ASJ AF: 0.559

Gnomad4 EAS AF: 0.489

Gnomad4 SAS AF: 0.658

Gnomad4 FIN AF: 0.705

Gnomad4 NFE AF: 0.667

Gnomad4 OTH AF: 0.673

Alfa AF: 0.675 Hom.: 6224

Bravo AF: 0.692

Asia WGS AF: 0.626 AC: 2177 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.99
DANN	Benign	0.50
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs550659; hg19: chr11-17925984;