Genetic Variant GIMAP6:p.Leu287Leu (chr7-150627737-C-T) – ACMG Classification: Benign (-15 pts)

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_024711.6(GIMAP6):c.861G>A(p.Leu287Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 1,613,202 control chromosomes in the GnomAD database, including 76,866 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.30 ( 6903 hom., cov: 32)

Exomes 𝑓: 0.31 ( 69963 hom. )

Consequence

GIMAP6
NM_024711.6 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.751

Variant links:

Genes affected

GIMAP6 (HGNC:21918): (GTPase, IMAP family member 6) This gene encodes a member of the GTPases of immunity-associated proteins (GIMAP) family. GIMAP proteins contain GTP-binding and coiled-coil motifs, and may play roles in the regulation of cell survival. Decreased expression of this gene may play a role in non-small cell lung cancer. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, which is found in a cluster with seven additional GIMAP genes on the long arm of chromosome 7. [provided by RefSeq, Sep 2011]

GIMAP6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 7-150627737-C-T is Benign according to our data. Variant chr7-150627737-C-T is described in ClinVar as [Benign]. Clinvar id is 2688170.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.751 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.307 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GIMAP6	NM_024711.6 link	c.861G>A	p.Leu287Leu	synonymous_variant	Exon 3 of 3	ENST00000328902.9	NP_078987.3	Q6P9H5-1A0A090N7V4
GIMAP6	NM_001244072.2 link	c.1071G>A	p.Leu357Leu	synonymous_variant	Exon 3 of 3		NP_001231001.1	Q6P9H5B4DH95
GIMAP6	NM_001244071.2 link	c.*448G>A		3_prime_UTR_variant	Exon 3 of 3		NP_001231000.1	Q6P9H5-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
GIMAP6	ENST00000328902.9 link	c.861G>A	p.Leu287Leu	synonymous_variant	Exon 3 of 3	1	NM_024711.6	ENSP00000330374.5	Q6P9H5-1
GIMAP6	ENST00000618759.4 link	c.1071G>A	p.Leu357Leu	synonymous_variant	Exon 3 of 3	2		ENSP00000479580.1	B4DH95
GIMAP6	ENST00000493969 link	c.*448G>A		3_prime_UTR_variant	Exon 3 of 3	2		ENSP00000418304.1	Q6P9H5-3

Frequencies

GnomAD3 genomes

AF:

0.299

AC:

45474

AN:

151944

Hom.:

6898

Cov.:

show subpopulations

Gnomad AFR

AF:

0.283

Gnomad AMI

AF:

0.255

Gnomad AMR

AF:

0.285

Gnomad ASJ

AF:

0.321

Gnomad EAS

AF:

0.318

Gnomad SAS

AF:

0.291

Gnomad FIN

AF:

0.303

Gnomad MID

AF:

0.293

Gnomad NFE

AF:

0.311

Gnomad OTH

AF:

0.298

GnomAD3 exomes

AF:

0.296

AC:

74279

AN:

250714

Hom.:

11124

AF XY:

0.299

AC XY:

40485

AN XY:

135490

show subpopulations

Gnomad AFR exome

AF:

0.282

Gnomad AMR exome

AF:

0.269

Gnomad ASJ exome

AF:

0.314

Gnomad EAS exome

AF:

0.306

Gnomad SAS exome

AF:

0.284

Gnomad FIN exome

AF:

0.292

Gnomad NFE exome

AF:

0.307

Gnomad OTH exome

AF:

0.300

GnomAD4 exome

AF:

0.309

AC:

450820

AN:

1461138

Hom.:

69963

Cov.:

AF XY:

0.309

AC XY:

224384

AN XY:

726832

show subpopulations

Gnomad4 AFR exome

AF:

0.276

Gnomad4 AMR exome

AF:

0.271

Gnomad4 ASJ exome

AF:

0.314

Gnomad4 EAS exome

AF:

0.334

Gnomad4 SAS exome

AF:

0.290

Gnomad4 FIN exome

AF:

0.290

Gnomad4 NFE exome

AF:

0.313

Gnomad4 OTH exome

AF:

0.301

GnomAD4 genome

AF:

0.299

AC:

45509

AN:

152064

Hom.:

6903

Cov.:

AF XY:

0.299

AC XY:

22252

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.282

Gnomad4 AMR

AF:

0.286

Gnomad4 ASJ

AF:

0.321

Gnomad4 EAS

AF:

0.318

Gnomad4 SAS

AF:

0.292

Gnomad4 FIN

AF:

0.303

Gnomad4 NFE

AF:

0.311

Gnomad4 OTH

AF:

0.301

Alfa

AF:

0.306

Hom.:

3912

Bravo

AF:

0.296

Asia WGS

AF:

0.288

AC:

998

AN:

3478

EpiCase

AF:

0.323

EpiControl

AF:

0.313

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 43% of patients studied by a panel of primary immunodeficiencies. Number of patients: 41. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.65

DANN

Benign

0.57

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over