chr1-92607683-C-T

Variant names:

• chr1-92607683-C-T
• rs141343784
• NM_001350197.2:c.1872G>A

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001350197.2(EVI5):​c.1872G>A​(p.Val624Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00927 in 1,605,500 control chromosomes in the GnomAD database, including 103 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0070 (9 hom., cov: 31)
  • Exomes 𝑓: 0.0095 (94 hom.)
• Consequence: EVI5 NM_001350197.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.167
• Publications: 4 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]

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 1-92607683-C-T is Benign according to our data. Variant chr1-92607683-C-T is described in ClinVar as Benign. ClinVar VariationId is 775568.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.167 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 9 AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EVI5	NM_001350197.2	MANE Select	c.1872G>A	p.Val624Val	synonymous	Exon 17 of 20	NP_001337126.1	A0A804HIC4
	EVI5	NM_001308248.2		c.1857G>A	p.Val619Val	synonymous	Exon 16 of 19	NP_001295177.1	O60447-2
	EVI5	NM_001377210.1		c.1848G>A	p.Val616Val	synonymous	Exon 16 of 19	NP_001364139.1	A0A9L9PXL1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EVI5	ENST00000684568.2	MANE Select	c.1872G>A	p.Val624Val	synonymous	Exon 17 of 20	ENSP00000506999.1	A0A804HIC4
	EVI5	ENST00000540033.3	TSL:1	c.1857G>A	p.Val619Val	synonymous	Exon 16 of 19	ENSP00000440826.2	O60447-2
	EVI5	ENST00000370331.5	TSL:1	c.1824G>A	p.Val608Val	synonymous	Exon 15 of 18	ENSP00000359356.1	O60447-1

Frequencies

GnomAD3 genomes AF: 0.00698 AC: 1061 AN: 152070 Hom.: 9 Cov.: 31

Gnomad AFR AF: 0.00251

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00642

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00332

Gnomad FIN AF: 0.00586

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0111

Gnomad OTH AF: 0.00813

GnomAD2 exomes AF: 0.00716 AC: 1754 AN: 244954 AF XY: 0.00732

Gnomad AFR exome AF: 0.00245

Gnomad AMR exome AF: 0.00361

Gnomad ASJ exome AF: 0.00532

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00603

Gnomad NFE exome AF: 0.0117

Gnomad OTH exome AF: 0.00856

GnomAD4 exome AF: 0.00951 AC: 13826 AN: 1453312 Hom.: 94 Cov.: 28 AF XY: 0.00951 AC XY: 6878 AN XY: 723006

African (AFR) AF: 0.00148 AC: 49 AN: 33128

American (AMR) AF: 0.00389 AC: 170 AN: 43726

Ashkenazi Jewish (ASJ) AF: 0.00369 AC: 96 AN: 26008

East Asian (EAS) AF: 0.00 AC: 0 AN: 39510

South Asian (SAS) AF: 0.00235 AC: 199 AN: 84712

European-Finnish (FIN) AF: 0.00793 AC: 418 AN: 52692

Middle Eastern (MID) AF: 0.00330 AC: 19 AN: 5754

European-Non Finnish (NFE) AF: 0.0112 AC: 12453 AN: 1107684

Other (OTH) AF: 0.00702 AC: 422 AN: 60098

GnomAD4 genome AF: 0.00697 AC: 1060 AN: 152188 Hom.: 9 Cov.: 31 AF XY: 0.00655 AC XY: 487 AN XY: 74390

African (AFR) AF: 0.00250 AC: 104 AN: 41528

American (AMR) AF: 0.00641 AC: 98 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00202 AC: 7 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5178

South Asian (SAS) AF: 0.00353 AC: 17 AN: 4812

European-Finnish (FIN) AF: 0.00586 AC: 62 AN: 10584

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0111 AC: 752 AN: 68014

Other (OTH) AF: 0.00805 AC: 17 AN: 2112

Alfa AF: 0.00979 Hom.: 4

Bravo AF: 0.00722

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	7.3
DANN	Benign	0.56
PhyloP100		-0.17
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs141343784; hg19: chr1-93073240; COSMIC: COSV64829867;