rs768834640

Variant names:

• chr19-13153491-C-A
• rs768834640
• NM_004907.3:c.305C>A

Your query was ambiguous. Multiple possible variants found:

• chr19-13153491-C-A
• chr19-13153491-C-G
• chr19-13153491-C-T

Variant summary

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

The NM_004907.3(IER2):​c.305C>A​(p.Pro102Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000697 in 1,434,406 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: IER2 NM_004907.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0180
• Publications: 0 publications found

Genes affected

IER2 (HGNC:28871): (immediate early response 2) Predicted to enable DNA binding activity. Involved in cell motility and positive regulation of transcription by RNA polymerase II. Located in cytoplasm and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000267598 (HGNC:58207):

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=0.09077069).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IER2	NM_004907.3	c.305C>A	p.Pro102Gln	missense_variant	Exon 2 of 2	ENST00000292433.4	NP_004898.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IER2	ENST00000292433.4	c.305C>A	p.Pro102Gln	missense_variant	Exon 2 of 2	1	NM_004907.3	ENSP00000292433.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.97e-7 AC: 1 AN: 1434406 Hom.: 0 Cov.: 31 AF XY: 0.00000141 AC XY: 1 AN XY: 711688

African (AFR) AF: 0.00 AC: 0 AN: 32730

American (AMR) AF: 0.00 AC: 0 AN: 41144

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25662

East Asian (EAS) AF: 0.00 AC: 0 AN: 37960

South Asian (SAS) AF: 0.00 AC: 0 AN: 83414

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48838

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5716

European-Non Finnish (NFE) AF: 9.09e-7 AC: 1 AN: 1099730

Other (OTH) AF: 0.00 AC: 0 AN: 59212

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	14
DANN	Benign	0.95
DEOGEN2	Benign	0.025	T;T;T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.037	N
LIST_S2	Benign	0.48	.;.;T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.091	T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.69	N;N;N
PhyloP100		-0.018
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-2.5	.;D;.
REVEL	Benign	0.11
Sift	Benign	0.31	.;T;.
Sift4G	Benign	0.32	T;T;T
Polyphen		0.35	B;B;B
Vest4		0.14
MutPred		0.54		Loss of glycosylation at T103 (P = 0.0487);Loss of glycosylation at T103 (P = 0.0487);Loss of glycosylation at T103 (P = 0.0487);
MVP		0.043
MPC		0.77
ClinPred		0.45	T
GERP RS		1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.061
gMVP		0.13
Mutation Taster		=98/2	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: rs768834640; hg19: chr19-13264305;