7-150627737-C-T

Variant names:

• chr7-150627737-C-T
• rs3735084
• NM_024711.6:c.861G>A

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.751
• Publications: 10 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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	c.861G>A	p.Leu287Leu	synonymous_variant	Exon 3 of 3	ENST00000328902.9	NP_078987.3
GIMAP6	NM_001244072.2	c.1071G>A	p.Leu357Leu	synonymous_variant	Exon 3 of 3		NP_001231001.1
GIMAP6	NM_001244071.2	c.*448G>A		3_prime_UTR_variant	Exon 3 of 3		NP_001231000.1

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.299 AC: 45474 AN: 151944 Hom.: 6898 Cov.: 32

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

GnomAD2 exomes AF: 0.296 AC: 74279 AN: 250714 AF XY: 0.299

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 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.: 41 AF XY: 0.309 AC XY: 224384 AN XY: 726832

African (AFR) AF: 0.276 AC: 9242 AN: 33464

American (AMR) AF: 0.271 AC: 12091 AN: 44678

Ashkenazi Jewish (ASJ) AF: 0.314 AC: 8191 AN: 26066

East Asian (EAS) AF: 0.334 AC: 13244 AN: 39690

South Asian (SAS) AF: 0.290 AC: 24956 AN: 86166

European-Finnish (FIN) AF: 0.290 AC: 15487 AN: 53390

Middle Eastern (MID) AF: 0.286 AC: 1651 AN: 5764

European-Non Finnish (NFE) AF: 0.313 AC: 347775 AN: 1111552

Other (OTH) AF: 0.301 AC: 18183 AN: 60368

GnomAD4 genome AF: 0.299 AC: 45509 AN: 152064 Hom.: 6903 Cov.: 32 AF XY: 0.299 AC XY: 22252 AN XY: 74336

African (AFR) AF: 0.282 AC: 11701 AN: 41466

American (AMR) AF: 0.286 AC: 4367 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.321 AC: 1114 AN: 3468

East Asian (EAS) AF: 0.318 AC: 1639 AN: 5154

South Asian (SAS) AF: 0.292 AC: 1407 AN: 4822

European-Finnish (FIN) AF: 0.303 AC: 3206 AN: 10578

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.311 AC: 21125 AN: 67976

Other (OTH) AF: 0.301 AC: 635 AN: 2110

Alfa AF: 0.305 Hom.: 5134

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

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
PhyloP100		0.75
Mutation Taster		=100/0	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: rs3735084; hg19: chr7-150324825; COSMIC: COSV61032514;