9-129177092-G-A

Variant names:

• chr9-129177092-G-A
• rs1176648199
• NM_203434.3:c.961C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_203434.3(IER5L):​c.961C>T​(p.Leu321Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000229 in 1,311,032 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000023 (0 hom.)
• Consequence: IER5L NM_203434.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.17
• Publications: 0 publications found

Genes affected

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

ENSG00000235007 (HGNC:):

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

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP7: Synonymous conserved (PhyloP=1.17 with no splicing effect.

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.961C>T	p.Leu321Leu	synonymous	Exon 1 of 1	NP_982258.2	Q5T953-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IER5L	ENST00000372491.4	TSL:6 MANE Select	c.961C>T	p.Leu321Leu	synonymous	Exon 1 of 1	ENSP00000361569.2	Q5T953-1
	ENSG00000235007	ENST00000674648.1		c.109-31777G>A		intron	N/A	ENSP00000502744.1	A0A6Q8PH23
	IER5L-AS1	ENST00000372490.4	TSL:2	n.322G>A		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000229 AC: 3 AN: 1311032 Hom.: 0 Cov.: 33 AF XY: 0.00000312 AC XY: 2 AN XY: 640416

African (AFR) AF: 0.00 AC: 0 AN: 25812

American (AMR) AF: 0.00 AC: 0 AN: 21024

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19424

East Asian (EAS) AF: 0.00 AC: 0 AN: 31894

South Asian (SAS) AF: 0.00 AC: 0 AN: 67146

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45500

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5180

European-Non Finnish (NFE) AF: 0.00000288 AC: 3 AN: 1041128

Other (OTH) AF: 0.00 AC: 0 AN: 53924

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	15
DANN	Benign	0.95
PhyloP100		1.2

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: rs1176648199; hg19: chr9-131939371;