chr17-31317834-G-A

Variant names:

• chr17-31317834-G-A
• rs7505
• NM_014210.4:c.*469C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014210.4(EVI2A):​c.*469C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.501 in 152,988 control chromosomes in the GnomAD database, including 20,966 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 0.50 (20794 hom., cov: 32)
  • Exomes 𝑓: 0.54 (172 hom.)
• Consequence: EVI2A NM_014210.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.43
• Publications: 15 publications found

Genes affected

EVI2A (HGNC:3499): (ecotropic viral integration site 2A) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

NF1 (HGNC:7765): (neurofibromin 1) This gene product appears to function as a negative regulator of the ras signal transduction pathway. Mutations in this gene have been linked to neurofibromatosis type 1, juvenile myelomonocytic leukemia and Watson syndrome. The mRNA for this gene is subject to RNA editing (CGA>UGA->Arg1306Term) resulting in premature translation termination. Alternatively spliced transcript variants encoding different isoforms have also been described for this gene. [provided by RefSeq, Jul 2008]

NF1 Gene-Disease associations (from GenCC):

• neurofibromatosis type 1

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, PanelApp Australia, G2P, Genomics England PanelApp
• neurofibromatosis-Noonan syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp, PanelApp Australia
• Moyamoya disease

  Inheritance: AD Classification: MODERATE Submitted by: Genomics England PanelApp
• hereditary pheochromocytoma-paraganglioma

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• familial ovarian cancer

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ENSG00000265118 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.615 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014210.4. 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
	EVI2A	NM_014210.4	MANE Select	c.*469C>T		3_prime_UTR	Exon 2 of 2	NP_055025.2
	NF1	NM_001042492.3	MANE Select	c.4836-7986G>A		intron	N/A	NP_001035957.1
	EVI2A	NM_001003927.3		c.*469C>T		3_prime_UTR	Exon 3 of 3	NP_001003927.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EVI2A	ENST00000462804.3	TSL:1 MANE Select	c.*469C>T		3_prime_UTR	Exon 2 of 2	ENSP00000420557.3
	NF1	ENST00000358273.9	TSL:1 MANE Select	c.4836-7986G>A		intron	N/A	ENSP00000351015.4
	NF1	ENST00000356175.7	TSL:1	c.4773-7986G>A		intron	N/A	ENSP00000348498.3

Frequencies

GnomAD3 genomes AF: 0.501 AC: 76012 AN: 151788 Hom.: 20786 Cov.: 32

Gnomad AFR AF: 0.287

Gnomad AMI AF: 0.678

Gnomad AMR AF: 0.445

Gnomad ASJ AF: 0.684

Gnomad EAS AF: 0.360

Gnomad SAS AF: 0.570

Gnomad FIN AF: 0.602

Gnomad MID AF: 0.605

Gnomad NFE AF: 0.620

Gnomad OTH AF: 0.532

GnomAD4 exome AF: 0.538 AC: 582 AN: 1082 Hom.: 172 Cov.: 0 AF XY: 0.534 AC XY: 314 AN XY: 588

African (AFR) AF: 0.167 AC: 2 AN: 12

American (AMR) AF: 0.371 AC: 26 AN: 70

Ashkenazi Jewish (ASJ) AF: 0.688 AC: 11 AN: 16

East Asian (EAS) AF: 0.250 AC: 2 AN: 8

South Asian (SAS) AF: 0.524 AC: 88 AN: 168

European-Finnish (FIN) AF: 0.556 AC: 10 AN: 18

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.569 AC: 427 AN: 750

Other (OTH) AF: 0.421 AC: 16 AN: 38

GnomAD4 genome AF: 0.501 AC: 76045 AN: 151906 Hom.: 20794 Cov.: 32 AF XY: 0.498 AC XY: 36981 AN XY: 74242

African (AFR) AF: 0.287 AC: 11905 AN: 41442

American (AMR) AF: 0.445 AC: 6783 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.684 AC: 2373 AN: 3470

East Asian (EAS) AF: 0.360 AC: 1858 AN: 5164

South Asian (SAS) AF: 0.568 AC: 2736 AN: 4818

European-Finnish (FIN) AF: 0.602 AC: 6337 AN: 10528

Middle Eastern (MID) AF: 0.603 AC: 176 AN: 292

European-Non Finnish (NFE) AF: 0.620 AC: 42144 AN: 67924

Other (OTH) AF: 0.529 AC: 1116 AN: 2108

Alfa AF: 0.586 Hom.: 31572

Bravo AF: 0.478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	14
DANN	Benign	0.39
PhyloP100		2.4
Mutation Taster		=97/3	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: rs7505; hg19: chr17-29644852;