9-129177273-G-A

Position:

• chr9-129177273-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_203434.3(IER5L):​c.780C>T​(p.Asp260Asp) variant causes a synonymous change. The variant allele was found at a frequency of 0.00401 in 1,478,240 control chromosomes in the GnomAD database, including 209 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.021 (125 hom., cov: 32)
  • Exomes 𝑓: 0.0020 (84 hom.)
• Consequence: IER5L NM_203434.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 5.16

Genes affected

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

ENSG00000235007 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 9-129177273-G-A is Benign according to our data. Variant chr9-129177273-G-A is described in ClinVar as [Benign]. Clinvar id is 774207.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.073 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IER5L	NM_203434.3	c.780C>T	p.Asp260Asp	synonymous_variant	1/1	ENST00000372491.4	NP_982258.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IER5L	ENST00000372491.4	c.780C>T	p.Asp260Asp	synonymous_variant	1/1	6	NM_203434.3	ENSP00000361569.2
ENSG00000235007	ENST00000674648.1	c.109-31596G>A		intron_variant				ENSP00000502744.1

Frequencies

GnomAD3 genomes AF: 0.0215 AC: 3267 AN: 152120 Hom.: 125 Cov.: 32

Gnomad AFR AF: 0.0753

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00602

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000413

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000353

Gnomad OTH AF: 0.0134

GnomAD3 exomes AF: 0.00596 AC: 771 AN: 129278 Hom.: 29 AF XY: 0.00416 AC XY: 302 AN XY: 72658

Gnomad AFR exome AF: 0.0795

Gnomad AMR exome AF: 0.00252

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000682

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000256

Gnomad OTH exome AF: 0.00215

GnomAD4 exome AF: 0.00201 AC: 2665 AN: 1326002 Hom.: 84 Cov.: 32 AF XY: 0.00176 AC XY: 1149 AN XY: 654016

Gnomad4 AFR exome AF: 0.0772

Gnomad4 AMR exome AF: 0.00418

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000149

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000192

Gnomad4 OTH exome AF: 0.00506

GnomAD4 genome AF: 0.0215 AC: 3270 AN: 152238 Hom.: 125 Cov.: 32 AF XY: 0.0202 AC XY: 1506 AN XY: 74466

Gnomad4 AFR AF: 0.0752

Gnomad4 AMR AF: 0.00601

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000353

Gnomad4 OTH AF: 0.0132

Alfa AF: 0.00365 Hom.: 5

Bravo AF: 0.0245

Asia WGS AF: 0.00433 AC: 15 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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	-0.59
CADD	Benign	12
DANN	Benign	0.96

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

Other links and lift over

dbSNP: rs60193826; hg19: chr9-131939552;