7-150572454-G-T

Variant names:

• chr7-150572454-G-T
• rs2293172
• NM_018326.3:c.384G>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018326.3(GIMAP4):​c.384G>T​(p.Glu128Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 1,613,836 control chromosomes in the GnomAD database, including 19,389 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.13 (1516 hom., cov: 32)
  • Exomes 𝑓: 0.15 (17873 hom.)
• Consequence: GIMAP4 NM_018326.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38

Genes affected

GIMAP4 (HGNC:21872): (GTPase, IMAP family member 4) This gene encodes a protein belonging to the GTP-binding superfamily and to the immuno-associated nucleotide (IAN) subfamily of nucleotide-binding proteins. The encoded protein of this gene may be negatively regulated by T-cell acute lymphocytic leukemia 1 (TAL1). In humans, the IAN subfamily genes are located in a cluster at 7q36.1. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.001820147).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.196 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GIMAP4	NM_018326.3	c.384G>T	p.Glu128Asp	missense_variant	Exon 3 of 3	ENST00000255945.4	NP_060796.1
GIMAP4	NM_001363532.2	c.426G>T	p.Glu142Asp	missense_variant	Exon 3 of 3		NP_001350461.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GIMAP4	ENST00000255945.4	c.384G>T	p.Glu128Asp	missense_variant	Exon 3 of 3	1	NM_018326.3	ENSP00000255945.2

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20504 AN: 152084 Hom.: 1518 Cov.: 32

Gnomad AFR AF: 0.0802

Gnomad AMI AF: 0.185

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.0936

Gnomad EAS AF: 0.206

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.148

GnomAD3 exomes AF: 0.148 AC: 37064 AN: 251092 Hom.: 2870 AF XY: 0.147 AC XY: 19902 AN XY: 135688

Gnomad AFR exome AF: 0.0802

Gnomad AMR exome AF: 0.133

Gnomad ASJ exome AF: 0.103

Gnomad EAS exome AF: 0.210

Gnomad SAS exome AF: 0.114

Gnomad FIN exome AF: 0.181

Gnomad NFE exome AF: 0.158

Gnomad OTH exome AF: 0.149

GnomAD4 exome AF: 0.153 AC: 224289 AN: 1461634 Hom.: 17873 Cov.: 34 AF XY: 0.152 AC XY: 110727 AN XY: 727130

Gnomad4 AFR exome AF: 0.0759

Gnomad4 AMR exome AF: 0.132

Gnomad4 ASJ exome AF: 0.100

Gnomad4 EAS exome AF: 0.202

Gnomad4 SAS exome AF: 0.114

Gnomad4 FIN exome AF: 0.181

Gnomad4 NFE exome AF: 0.158

Gnomad4 OTH exome AF: 0.147

GnomAD4 genome AF: 0.135 AC: 20510 AN: 152202 Hom.: 1516 Cov.: 32 AF XY: 0.135 AC XY: 10081 AN XY: 74408

Gnomad4 AFR AF: 0.0800

Gnomad4 AMR AF: 0.131

Gnomad4 ASJ AF: 0.0936

Gnomad4 EAS AF: 0.206

Gnomad4 SAS AF: 0.112

Gnomad4 FIN AF: 0.188

Gnomad4 NFE AF: 0.158

Gnomad4 OTH AF: 0.150

Alfa AF: 0.149 Hom.: 4345

Bravo AF: 0.128

TwinsUK AF: 0.147 AC: 546

ALSPAC AF: 0.159 AC: 612

ESP6500AA AF: 0.0790 AC: 348

ESP6500EA AF: 0.157 AC: 1353

ExAC AF: 0.147 AC: 17810

Asia WGS AF: 0.176 AC: 614 AN: 3478

EpiCase AF: 0.151

EpiControl AF: 0.149

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	3.4
DANN	Benign	0.94
DEOGEN2	Benign	0.038	T;.;.
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.061	N
LIST_S2	Benign	0.069	T;T;T
MetaRNN	Benign	0.0018	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L;.;.
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.4	N;N;N
REVEL	Benign	0.068
Sift	Benign	0.41	T;T;T
Sift4G	Benign	0.62	T;T;T
Polyphen		0.0080	B;B;.
Vest4		0.097
MutPred		0.40		.;Gain of loop (P = 0.069);Gain of loop (P = 0.069);
MPC		0.055
ClinPred		0.0032	T
GERP RS		2.9
Varity_R		0.21
gMVP		0.46

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2293172; hg19: chr7-150269542; COSMIC: COSV99750479;