chr1-92580420-T-C

Variant names:

• chr1-92580420-T-C
• rs17380378
• NM_001350197.2:c.2071-16683A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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]

LOC107985727 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001350197.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EVI5	NM_001350197.2	MANE Select	c.2071-16683A>G		intron	N/A	NP_001337126.1
	EVI5	NM_001308248.2		c.2056-16683A>G		intron	N/A	NP_001295177.1
	EVI5	NM_001377210.1		c.2047-16683A>G		intron	N/A	NP_001364139.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EVI5	ENST00000684568.2	MANE Select	c.2071-16683A>G		intron	N/A	ENSP00000506999.1
	EVI5	ENST00000540033.3	TSL:1	c.2056-16683A>G		intron	N/A	ENSP00000440826.2
	EVI5	ENST00000370331.5	TSL:1	c.2023-16683A>G		intron	N/A	ENSP00000359356.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.143 AC: 34 AN: 238

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 4

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.0187 AC: 777 AN: 41572

American (AMR) AF: 0.0649 AC: 993 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0715 AC: 248 AN: 3468

East Asian (EAS) AF: 0.000385 AC: 2 AN: 5192

South Asian (SAS) AF: 0.0151 AC: 73 AN: 4828

European-Finnish (FIN) AF: 0.118 AC: 1248 AN: 10590

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.102 AC: 6934 AN: 68010

Other (OTH) AF: 0.0744 AC: 157 AN: 2110

Alfa AF: 0.0745 Hom.: 70

Bravo AF: 0.0639

Asia WGS AF: 0.00895 AC: 32 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.5
DANN	Benign	0.77
PhyloP100		-0.76
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: rs17380378; hg19: chr1-93045977;