7-150720269-T-C

Position:

chr7-150720269-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_130759.4(GIMAP1):c.265T>C(p.Ser89Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00113 in 1,614,056 control chromosomes in the GnomAD database, including 19 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 (★★).

Frequency

Genomes: 𝑓 0.0064 ( 10 hom., cov: 33)

Exomes 𝑓: 0.00059 ( 9 hom. )

Consequence

GIMAP1
NM_130759.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.00400

Variant links:

Genes affected

GIMAP1 (HGNC:23237): (GTPase, IMAP family member 1) 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 is thought to be involved in the differentiation of T helper (Th) cells of the Th1 lineage, and the related mouse gene has been shown to be critical for the development of mature B and T lymphocytes. Read-through transcription exists between this gene and the downstream GIMAP5 (GTPase, IMAP family member 5) gene. [provided by RefSeq, Dec 2010]

GIMAP1 links:

GIMAP1-GIMAP5 (HGNC:):

GIMAP1-GIMAP5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0031946301).

BP6

Variant 7-150720269-T-C is Benign according to our data. Variant chr7-150720269-T-C is described in ClinVar as [Benign]. Clinvar id is 789594.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00637 (969/152178) while in subpopulation AFR AF= 0.0224 (929/41508). AF 95% confidence interval is 0.0212. There are 10 homozygotes in gnomad4. There are 455 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 10 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
GIMAP1	NM_130759.4 linkuse as main transcript	c.265T>C	p.Ser89Pro	missense_variant	3/3	ENST00000307194.6	NP_570115.1
GIMAP1-GIMAP5	NM_001199577.2 linkuse as main transcript	c.265T>C	p.Ser89Pro	missense_variant	3/6		NP_001186506.1
GIMAP1-GIMAP5	NM_001303630.2 linkuse as main transcript	c.18+1179T>C		intron_variant			NP_001290559.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GIMAP1	ENST00000307194.6 linkuse as main transcript	c.265T>C	p.Ser89Pro	missense_variant	3/3	1	NM_130759.4	ENSP00000302833	P1

Frequencies

GnomAD3 genomes

AF:

0.00637

AC:

968

AN:

152060

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0224

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00177

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00165

AC:

415

AN:

251156

Hom.:

AF XY:

0.00125

AC XY:

170

AN XY:

135852

show subpopulations

Gnomad AFR exome

AF:

0.0232

Gnomad AMR exome

AF:

0.000752

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000705

Gnomad OTH exome

AF:

0.000490

GnomAD4 exome

AF:

0.000588

AC:

859

AN:

1461878

Hom.:

Cov.:

AF XY:

0.000487

AC XY:

354

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.0219

Gnomad4 AMR exome

AF:

0.000850

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000189

Gnomad4 OTH exome

AF:

0.00103

GnomAD4 genome

AF:

0.00637

AC:

969

AN:

152178

Hom.:

Cov.:

AF XY:

0.00612

AC XY:

455

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.0224

Gnomad4 AMR

AF:

0.00176

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00110

Hom.:

Bravo

AF:

0.00704

ESP6500AA

AF:

0.0216

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00210

AC:

255

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 08, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.61

CADD

Benign

5.7

DANN

Benign

0.84

DEOGEN2

Benign

0.018

T;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.027

LIST_S2

Benign

0.27

T;T

MetaRNN

Benign

0.0032

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.0

L;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.38

PROVEAN

Uncertain

-2.4

N;.

REVEL

Benign

0.073

Sift

Benign

0.23

T;.

Sift4G

Benign

0.31

T;D

Polyphen

0.0010

B;.

Vest4

0.023

MVP

0.17

MPC

0.89

ClinPred

0.0029

GERP RS

-4.9

Varity_R

0.51

gMVP

0.61

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