Genetic Variant GIMAP5:n.746C>T (chr7-150738355-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000476324.1(GIMAP5):n.746C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 152,480 control chromosomes in the GnomAD database, including 11,761 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.38 ( 11736 hom., cov: 31)

Exomes 𝑓: 0.31 ( 25 hom. )

Consequence

GIMAP5
ENST00000476324.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.08

Publications

4 publications found

Variant links:

Genes affected

GIMAP5 (HGNC:18005): (GTPase, IMAP family member 5) 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. This gene encodes an antiapoptotic protein that functions in T-cell survival. Polymorphisms in this gene are associated with systemic lupus erythematosus. Read-through transcription exists between this gene and the neighboring upstream GIMAP1 (GTPase, IMAP family member 1) gene. [provided by RefSeq, Dec 2010]

GIMAP5 links:

GIMAP1-GIMAP5 (HGNC:51257): (GIMAP1-GIMAP5 readthrough) This locus represents naturally occurring readthrough transcription between the neighboring GIMAP1 (GTPase, IMAP family member 1) and GIMAP5 (GTPase, IMAP family member 5) genes on chromosome 7. Alternative splicing results in multiple readthrough transcript variants, one of which encodes a fusion protein that shares sequence identity with each individual gene product. [provided by RefSeq, Jan 2015]

GIMAP1-GIMAP5 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.534 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
GIMAP5	NM_018384.5 link	c.-7+647C>T	intron_variant	Intron 1 of 2	ENST00000358647.5	NP_060854.2	Q96F15-1A0A090N8P9
GIMAP1-GIMAP5	NM_001199577.2 link	c.606+647C>T	intron_variant	Intron 4 of 5		NP_001186506.1	A0A087WTJ2
GIMAP1-GIMAP5	NM_001303630.2 link	c.222+647C>T	intron_variant	Intron 3 of 4		NP_001290559.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GIMAP5	ENST00000358647.5 link	c.-7+647C>T		intron_variant	Intron 1 of 2	1	NM_018384.5	ENSP00000351473.3		Q96F15-1
GIMAP1-GIMAP5	ENST00000611999.4 link	c.606+647C>T		intron_variant	Intron 4 of 5	5		ENSP00000477920.1		A0A087WTJ2

Frequencies

GnomAD3 genomes

AF:

0.376

AC:

57139

AN:

151788

Hom.:

11719

Cov.:

show subpopulations

Gnomad AFR

AF:

0.540

Gnomad AMI

AF:

0.164

Gnomad AMR

AF:

0.282

Gnomad ASJ

AF:

0.336

Gnomad EAS

AF:

0.273

Gnomad SAS

AF:

0.375

Gnomad FIN

AF:

0.401

Gnomad MID

AF:

0.351

Gnomad NFE

AF:

0.308

Gnomad OTH

AF:

0.346

GnomAD4 exome

AF:

0.314

AC:

180

AN:

574

Hom.:

Cov.:

AF XY:

0.343

AC XY:

AN XY:

280

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AF:

0.289

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.250

AC:

AN:

European-Finnish (FIN)

AF:

0.250

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.314

AC:

145

AN:

462

Other (OTH)

AF:

0.400

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.377

AC:

57205

AN:

151906

Hom.:

11736

Cov.:

AF XY:

0.379

AC XY:

28110

AN XY:

74208

show subpopulations

African (AFR)

AF:

0.540

AC:

22354

AN:

41384

American (AMR)

AF:

0.281

AC:

4300

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.336

AC:

1167

AN:

3470

East Asian (EAS)

AF:

0.273

AC:

1406

AN:

5150

South Asian (SAS)

AF:

0.375

AC:

1806

AN:

4820

European-Finnish (FIN)

AF:

0.401

AC:

4221

AN:

10528

Middle Eastern (MID)

AF:

0.364

AC:

107

AN:

294

European-Non Finnish (NFE)

AF:

0.308

AC:

20961

AN:

67962

Other (OTH)

AF:

0.348

AC:

734

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1752

3504

5255

7007

8759

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

536

1072

1608

2144

2680

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.231

Hom.:

558

Bravo

AF:

0.372

Asia WGS

AF:

0.331

AC:

1154

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

4.1

(source)

DANN

Benign

0.49

PhyloP100

-1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over