7-150627888-T-C

Variant names:

• chr7-150627888-T-C
• rs11977216
• NM_024711.6:c.710A>G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_024711.6(GIMAP6):​c.710A>G​(p.Gln237Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00583 in 1,614,240 control chromosomes in the GnomAD database, including 506 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.031 (285 hom., cov: 33)
  • Exomes 𝑓: 0.0032 (221 hom.)
• Consequence: GIMAP6 NM_024711.6 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.427

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

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0017630458).
• BP6: Variant 7-150627888-T-C is Benign according to our data. Variant chr7-150627888-T-C is described in ClinVar as [Benign]. Clinvar id is 776269.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GIMAP6	NM_024711.6	c.710A>G	p.Gln237Arg	missense_variant	Exon 3 of 3	ENST00000328902.9	NP_078987.3
GIMAP6	NM_001244072.2	c.920A>G	p.Gln307Arg	missense_variant	Exon 3 of 3		NP_001231001.1
GIMAP6	NM_001244071.2	c.*297A>G		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.710A>G	p.Gln237Arg	missense_variant	Exon 3 of 3	1	NM_024711.6	ENSP00000330374.5
GIMAP6	ENST00000618759.4	c.920A>G	p.Gln307Arg	missense_variant	Exon 3 of 3	2		ENSP00000479580.1
GIMAP6	ENST00000493969	c.*297A>G		3_prime_UTR_variant	Exon 3 of 3	2		ENSP00000418304.1

Frequencies

GnomAD3 genomes AF: 0.0308 AC: 4687 AN: 152240 Hom.: 285 Cov.: 33

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0118

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000382

Gnomad OTH AF: 0.0196

GnomAD3 exomes AF: 0.00822 AC: 2066 AN: 251314 Hom.: 94 AF XY: 0.00604 AC XY: 820 AN XY: 135820

Gnomad AFR exome AF: 0.108

Gnomad AMR exome AF: 0.00651

Gnomad ASJ exome AF: 0.000795

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000653

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000378

Gnomad OTH exome AF: 0.00489

GnomAD4 exome AF: 0.00323 AC: 4729 AN: 1461882 Hom.: 221 Cov.: 33 AF XY: 0.00282 AC XY: 2051 AN XY: 727246

Gnomad4 AFR exome AF: 0.111

Gnomad4 AMR exome AF: 0.00637

Gnomad4 ASJ exome AF: 0.000459

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000174

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000225

Gnomad4 OTH exome AF: 0.00702

GnomAD4 genome AF: 0.0308 AC: 4689 AN: 152358 Hom.: 285 Cov.: 33 AF XY: 0.0296 AC XY: 2207 AN XY: 74508

Gnomad4 AFR AF: 0.107

Gnomad4 AMR AF: 0.0118

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000382

Gnomad4 OTH AF: 0.0194

Alfa AF: 0.00575 Hom.: 102

Bravo AF: 0.0358

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.109 AC: 479

ESP6500EA AF: 0.000465 AC: 4

ExAC AF: 0.0100 AC: 1214

Asia WGS AF: 0.00549 AC: 20 AN: 3478

EpiCase AF: 0.000545

EpiControl AF: 0.000711

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 02, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.67	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	0.14
DANN	Benign	0.21
DEOGEN2	Benign	0.00080	T;.
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.052	N
LIST_S2	Benign	0.29	T;T
MetaRNN	Benign	0.0018	T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.85	L;.
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-1.0	N;.
REVEL	Benign	0.017
Sift	Benign	0.49	T;.
Sift4G	Benign	0.58	T;T
Polyphen		0.0020	B;.
Vest4		0.047
MVP		0.092
MPC		0.14
ClinPred		0.0013	T
GERP RS		-0.0074
Varity_R		0.062
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: rs11977216; hg19: chr7-150324976;