Variant 9-129177372-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_203434.3(IER5L):c.681G>T(p.Pro227Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000953 in 818,392 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0035 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00045 ( 2 hom. )

Consequence

IER5L
NM_203434.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.354

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 made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 9-129177372-C-A is Benign according to our data. Variant chr9-129177372-C-A is described in ClinVar as [Benign]. Clinvar id is 778454.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.354 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.000448 (305/681354) while in subpopulation AFR AF= 0.0195 (274/14076). AF 95% confidence interval is 0.0176. There are 2 homozygotes in gnomad4_exome. There are 139 alleles in male gnomad4_exome subpopulation. Median coverage is 28. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IER5L	NM_203434.3 link	c.681G>T	p.Pro227Pro	synonymous_variant	1/1	ENST00000372491.4	NP_982258.2	Q5T953-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IER5L	ENST00000372491.4 link	c.681G>T	p.Pro227Pro	synonymous_variant	1/1	6	NM_203434.3	ENSP00000361569.2		Q5T953-1
ENSG00000235007	ENST00000674648.1 link	c.109-31497C>A		intron_variant				ENSP00000502744.1		A0A6Q8PH23

Frequencies

GnomAD3 genomes

AF:

0.00347

AC:

475

AN:

136960

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0122

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000784

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:

0.0000317

Gnomad OTH

AF:

0.00156

GnomAD3 exomes

AF:

0.000859

AC:

AN:

80316

Hom.:

AF XY:

0.000672

AC XY:

AN XY:

46154

show subpopulations

Gnomad AFR exome

AF:

0.0108

Gnomad AMR exome

AF:

0.000230

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000223

Gnomad OTH exome

AF:

0.00144

GnomAD4 exome

AF:

0.000448

AC:

305

AN:

681354

Hom.:

Cov.:

AF XY:

0.000428

AC XY:

139

AN XY:

324732

show subpopulations

Gnomad4 AFR exome

AF:

0.0195

Gnomad4 AMR exome

AF:

0.000613

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000509

Gnomad4 OTH exome

AF:

0.000947

GnomAD4 genome

AF:

0.00347

AC:

475

AN:

137038

Hom.:

Cov.:

AF XY:

0.00328

AC XY:

219

AN XY:

66778

show subpopulations

Gnomad4 AFR

AF:

0.0121

Gnomad4 AMR

AF:

0.000782

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000317

Gnomad4 OTH

AF:

0.00155

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.94

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over