NM_153236.4:c.247C>T

Variant names:

• chr7-150520221-C-T
• rs3735080
• NM_153236.4:c.247C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_153236.4(GIMAP7):​c.247C>T​(p.Arg83Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 1,613,840 control chromosomes in the GnomAD database, including 43,711 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.19 (3501 hom., cov: 32)
  • Exomes 𝑓: 0.23 (40210 hom.)
• Consequence: GIMAP7 NM_153236.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.09
• Publications: 46 publications found

Genes affected

GIMAP7 (HGNC:22404): (GTPase, IMAP family member 7) This gene encodes a protein belonging to the GTP-binding superfamily and to the immuno-associated nucleotide (IAN) subfamily of nucleotide-binding proteins. In humans, the IAN subfamily genes are located in a cluster at 7q36.1. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.015388012).
• BP6: Variant 7-150520221-C-T is Benign according to our data. Variant chr7-150520221-C-T is described in ClinVar as Benign. ClinVar VariationId is 1294549.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.261 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153236.4. 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
	GIMAP7	NM_153236.4	MANE Select	c.247C>T	p.Arg83Cys	missense	Exon 2 of 2	NP_694968.1	Q8NHV1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GIMAP7	ENST00000313543.5	TSL:1 MANE Select	c.247C>T	p.Arg83Cys	missense	Exon 2 of 2	ENSP00000315474.4	Q8NHV1
	GIMAP7	ENST00000955193.1		c.247C>T	p.Arg83Cys	missense	Exon 2 of 2	ENSP00000625252.1
	GIMAP7	ENST00000955194.1		c.247C>T	p.Arg83Cys	missense	Exon 3 of 3	ENSP00000625253.1

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28834 AN: 152004 Hom.: 3504 Cov.: 32

Gnomad AFR AF: 0.0445

Gnomad AMI AF: 0.284

Gnomad AMR AF: 0.268

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.233

Gnomad FIN AF: 0.339

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.233

Gnomad OTH AF: 0.168

GnomAD2 exomes AF: 0.235 AC: 58956 AN: 251096 AF XY: 0.236

Gnomad AFR exome AF: 0.0395

Gnomad AMR exome AF: 0.315

Gnomad ASJ exome AF: 0.256

Gnomad EAS exome AF: 0.153

Gnomad FIN exome AF: 0.333

Gnomad NFE exome AF: 0.230

Gnomad OTH exome AF: 0.235

GnomAD4 exome AF: 0.231 AC: 337032 AN: 1461718 Hom.: 40210 Cov.: 54 AF XY: 0.231 AC XY: 167883 AN XY: 727150

African (AFR) AF: 0.0374 AC: 1251 AN: 33480

American (AMR) AF: 0.311 AC: 13916 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.257 AC: 6717 AN: 26134

East Asian (EAS) AF: 0.164 AC: 6495 AN: 39698

South Asian (SAS) AF: 0.240 AC: 20705 AN: 86246

European-Finnish (FIN) AF: 0.329 AC: 17588 AN: 53398

Middle Eastern (MID) AF: 0.193 AC: 1114 AN: 5768

European-Non Finnish (NFE) AF: 0.230 AC: 255573 AN: 1111906

Other (OTH) AF: 0.226 AC: 13673 AN: 60386

GnomAD4 genome AF: 0.190 AC: 28831 AN: 152122 Hom.: 3501 Cov.: 32 AF XY: 0.196 AC XY: 14548 AN XY: 74358

African (AFR) AF: 0.0445 AC: 1848 AN: 41524

American (AMR) AF: 0.267 AC: 4090 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.267 AC: 926 AN: 3470

East Asian (EAS) AF: 0.151 AC: 781 AN: 5176

South Asian (SAS) AF: 0.232 AC: 1117 AN: 4820

European-Finnish (FIN) AF: 0.339 AC: 3582 AN: 10556

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.233 AC: 15822 AN: 67970

Other (OTH) AF: 0.167 AC: 353 AN: 2108

Alfa AF: 0.210 Hom.: 12435

Bravo AF: 0.179

TwinsUK AF: 0.224 AC: 831

ALSPAC AF: 0.217 AC: 836

ESP6500AA AF: 0.0495 AC: 218

ESP6500EA AF: 0.228 AC: 1961

ExAC AF: 0.226 AC: 27395

Asia WGS AF: 0.172 AC: 599 AN: 3478

EpiCase AF: 0.222

EpiControl AF: 0.221

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.063	T
Eigen	Benign	-0.85
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.027	N
LIST_S2	Uncertain	0.87	D
MetaRNN	Benign	0.015	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Pathogenic	3.7	H
PhyloP100		-1.1
PrimateAI	Benign	0.24	T
PROVEAN	Pathogenic	-6.2	D
REVEL	Benign	0.14
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.093
MPC		0.83
ClinPred		0.14	T
GERP RS		-10
Varity_R		0.43
gMVP		0.20
Mutation Taster		=86/14	polymorphism (auto)

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: rs3735080; hg19: chr7-150217309; COSMIC: COSV57958428;