dbSNP rs773744257: IER5L:p.Asp317Asn (chr9-129177104-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_203434.3(IER5L):c.949G>A(p.Asp317Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000411 in 1,459,736 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000031 ( 0 hom. )

Consequence

IER5L
NM_203434.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.34

Publications

0 publications found

Variant links:

Genes affected

IER5L (HGNC:23679): (immediate early response 5 like)

IER5L links:

ENSG00000235007 (HGNC:):

ENSG00000235007 links:

IER5L-AS1 (HGNC:55825): (IER5L antisense RNA 1)

IER5L-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15220287).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_203434.3. 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
	IER5L	NM_203434.3	MANE Select	c.949G>A	p.Asp317Asn	missense	Exon 1 of 1	NP_982258.2	Q5T953-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IER5L	ENST00000372491.4	TSL:6 MANE Select	c.949G>A	p.Asp317Asn	missense	Exon 1 of 1	ENSP00000361569.2	Q5T953-1
ENSG00000235007	ENST00000674648.1		c.109-31765C>T		intron	N/A	ENSP00000502744.1	A0A6Q8PH23
IER5L-AS1	ENST00000372490.4	TSL:2	n.334C>T		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000136

AC:

AN:

73352

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000328

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000306

AC:

AN:

1307612

Hom.:

Cov.:

AF XY:

0.00000470

AC XY:

AN XY:

638384

show subpopulations

African (AFR)

AF:

0.0000387

AC:

AN:

25830

American (AMR)

AF:

0.00

AC:

AN:

20296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18978

East Asian (EAS)

AF:

0.0000311

AC:

AN:

32146

South Asian (SAS)

AF:

0.00

AC:

AN:

66018

European-Finnish (FIN)

AF:

0.00

AC:

AN:

45474

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5196

European-Non Finnish (NFE)

AF:

0.00000192

AC:

AN:

1039856

Other (OTH)

AF:

0.00

AC:

AN:

53818

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.538

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152124

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.0000483

AC:

AN:

41440

American (AMR)

AF:

0.00

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5152

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68000

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.00000885

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.54

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0023

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.16

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.61

M_CAP

Uncertain

0.13

MetaRNN

Benign

0.15

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.90

PhyloP100

4.3

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-0.82

REVEL

Benign

0.082

Sift

Benign

0.13

Sift4G

Benign

0.57

Polyphen

0.41

Vest4

0.17

MutPred

0.39

Gain of helix (P = 0.0325)

MVP

0.13

MPC

0.88

ClinPred

0.45

GERP RS

3.1

Varity_R

0.15

gMVP

0.25

Mutation Taster

=90/10

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over