3-50288444-C-T

Variant names:

• chr3-50288444-C-T
• rs376948252
• NM_006764.5:c.1213G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006764.5(IFRD2):​c.1213G>A​(p.Ala405Thr) 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. 16/22 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. A405S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: IFRD2 NM_006764.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.02
• Publications: 0 publications found

Genes affected

IFRD2 (HGNC:5457): (interferon related developmental regulator 2) Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.055676997).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006764.5. 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
	IFRD2	NM_006764.5	MANE Select	c.1213G>A	p.Ala405Thr	missense	Exon 11 of 12	NP_006755.5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFRD2	ENST00000417626.8	TSL:1 MANE Select	c.1213G>A	p.Ala405Thr	missense	Exon 11 of 12	ENSP00000402849.4	Q12894
	IFRD2	ENST00000921977.1		c.1234G>A	p.Ala412Thr	missense	Exon 11 of 12	ENSP00000592036.1
	IFRD2	ENST00000879012.1		c.1225G>A	p.Ala409Thr	missense	Exon 11 of 12	ENSP00000549071.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	12
DANN	Benign	0.73
DEOGEN2	Benign	0.0072	T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.056	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.71	N
PhyloP100		1.0
PrimateAI	Benign	0.43	T
PROVEAN	Benign	0.96	N
REVEL	Benign	0.050
Sift	Benign	0.97	T
Sift4G	Benign	0.81	T
Polyphen		0.046	B
Vest4		0.12
MVP		0.31
ClinPred		0.41	T
GERP RS		5.1
PromoterAI		-0.0016	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.021
gMVP		0.16
Mutation Taster		=81/19	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: rs376948252; hg19: chr3-50325875;