chr1-181089206-C-G

Variant names:

• chr1-181089206-C-G
• rs375573233
• NM_016545.5:c.304C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016545.5(IER5):​c.304C>G​(p.Pro102Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P102L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: IER5 NM_016545.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0690
• Publications: 0 publications found

Genes affected

IER5 (HGNC:5393): (immediate early response 5) This gene encodes a protein that is similar to other immediate early response proteins. In the mouse, a similar gene may play an important role in mediating the cellular response to mitogenic signals. Studies in rats found the expression of a similar gene to be increased after waking and sleep deprivation. [provided by RefSeq, Jul 2008]

ACMG classification

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=0.11725283).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IER5	NM_016545.5	c.304C>G	p.Pro102Ala	missense_variant	Exon 1 of 1	ENST00000367577.7	NP_057629.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IER5	ENST00000367577.7	c.304C>G	p.Pro102Ala	missense_variant	Exon 1 of 1	6	NM_016545.5	ENSP00000356549.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	17
DANN	Benign	0.94
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.42	T
M_CAP	Pathogenic	0.31	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
PhyloP100		-0.069
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.043
Sift	Benign	0.10	T
Sift4G	Benign	0.30	T
Polyphen		0.39	B
Vest4		0.086
MutPred		0.50		Loss of glycosylation at P102 (P = 0.0247);
MVP		0.043
MPC		1.1
ClinPred		0.18	T
GERP RS		1.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.3
Varity_R		0.038
gMVP		0.094
Mutation Taster		=90/10	polymorphism

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: rs375573233; hg19: chr1-181058342;