rs307896

Positions:

• chr19-47158236-G-A
• chr19-47158236-G-C

Variant summary

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

The ENST00000270225.12(SAE1):​c.627+3023G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 152,034 control chromosomes in the GnomAD database, including 3,652 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 (3652 hom., cov: 32)
• Consequence: SAE1 ENST00000270225.12 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24

Genes affected

SAE1 (HGNC:30660): (SUMO1 activating enzyme subunit 1) Posttranslational modification of proteins by the addition of the small protein SUMO (see SUMO1; MIM 601912), or sumoylation, regulates protein structure and intracellular localization. SAE1 and UBA2 (MIM 613295) form a heterodimer that functions as a SUMO-activating enzyme for the sumoylation of proteins (Okuma et al., 1999 [PubMed 9920803]).[supplied by OMIM, Mar 2010]

LOC124904730 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SAE1	NM_005500.3	c.627+3023G>A		intron_variant		ENST00000270225.12	NP_005491.1
LOC124904730	XR_007067277.1	n.513-160G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SAE1	ENST00000270225.12	c.627+3023G>A		intron_variant		1	NM_005500.3	ENSP00000270225	P1

Frequencies

GnomAD3 genomes AF: 0.191 AC: 28992 AN: 151916 Hom.: 3653 Cov.: 32

Gnomad AFR AF: 0.0512

Gnomad AMI AF: 0.285

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.223

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0776

Gnomad FIN AF: 0.256

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.289

Gnomad OTH AF: 0.206

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

GnomAD4 genome AF: 0.191 AC: 28982 AN: 152034 Hom.: 3652 Cov.: 32 AF XY: 0.185 AC XY: 13730 AN XY: 74272

Gnomad4 AFR AF: 0.0511

Gnomad4 AMR AF: 0.169

Gnomad4 ASJ AF: 0.223

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0779

Gnomad4 FIN AF: 0.256

Gnomad4 NFE AF: 0.289

Gnomad4 OTH AF: 0.204

Alfa AF: 0.266 Hom.: 11168

Bravo AF: 0.180

Asia WGS AF: 0.0490 AC: 171 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	2.5
DANN	Benign	0.67

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: rs307896; hg19: chr19-47661493;