7-150720269-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.00400

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-GIMAP5 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 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 GnomAd at 10 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GIMAP1	NM_130759.4	c.265T>C	p.Ser89Pro	missense_variant	3/3	ENST00000307194.6
GIMAP1-GIMAP5	NM_001199577.2	c.265T>C	p.Ser89Pro	missense_variant	3/6
GIMAP1-GIMAP5	NM_001303630.2	c.18+1179T>C		intron_variant

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.00637 AC: 968 AN: 152060 Hom.: 10 Cov.: 33

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.: 2 AF XY: 0.00125 AC XY: 170 AN XY: 135852

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.: 9 Cov.: 31 AF XY: 0.000487 AC XY: 354 AN XY: 727240

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.: 10 Cov.: 33 AF XY: 0.00612 AC XY: 455 AN XY: 74400

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.: 2

Bravo AF: 0.00704

ESP6500AA AF: 0.0216 AC: 95

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00210 AC: 255

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 08, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.59	T
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	N
LIST_S2	Benign	0.27	T;T
MetaRNN	Benign	0.0032	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L;.
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.38	T
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	T
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

Other links and lift over

dbSNP: rs61748272; hg19: chr7-150417357;