rs17380378

Positions:

• chr1-92580420-T-C

Variant summary

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

The NM_001350197.2(EVI5):​c.2071-16683A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0696 in 152,522 control chromosomes in the GnomAD database, including 483 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 0.069 (480 hom., cov: 33)
  • Exomes 𝑓: 0.14 (3 hom.)
• Consequence: EVI5 NM_001350197.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.758

Genes affected

EVI5 (HGNC:3501): (ecotropic viral integration site 5) Enables GTPase activator activity and small GTPase binding activity. Involved in positive regulation of GTPase activity and retrograde transport, endosome to Golgi. Located in cytosol. [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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0999 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EVI5	NM_001350197.2	c.2071-16683A>G		intron_variant		ENST00000684568.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EVI5	ENST00000684568.2	c.2071-16683A>G		intron_variant			NM_001350197.2	P1

Frequencies

GnomAD3 genomes AF: 0.0696 AC: 10587 AN: 152162 Hom.: 482 Cov.: 33

Gnomad AFR AF: 0.0187

Gnomad AMI AF: 0.136

Gnomad AMR AF: 0.0650

Gnomad ASJ AF: 0.0715

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.0151

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.0761

GnomAD4 exome AF: 0.140 AC: 34 AN: 242 Hom.: 3 AF XY: 0.129 AC XY: 16 AN XY: 124

Gnomad4 FIN exome AF: 0.143

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.0695 AC: 10580 AN: 152280 Hom.: 480 Cov.: 33 AF XY: 0.0683 AC XY: 5082 AN XY: 74450

Gnomad4 AFR AF: 0.0187

Gnomad4 AMR AF: 0.0649

Gnomad4 ASJ AF: 0.0715

Gnomad4 EAS AF: 0.000385

Gnomad4 SAS AF: 0.0151

Gnomad4 FIN AF: 0.118

Gnomad4 NFE AF: 0.102

Gnomad4 OTH AF: 0.0744

Alfa AF: 0.0771 Hom.: 70

Bravo AF: 0.0639

Asia WGS AF: 0.00895 AC: 32 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.5
DANN	Benign	0.77

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: rs17380378; hg19: chr1-93045977;