rs4725936

Variant names:

• chr7-150741001-T-C
• rs4725936
• NM_018384.5:c.43+74T>C

Your query was ambiguous. Multiple possible variants found:

• chr7-150741001-T-C
• chr7-150741001-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018384.5(GIMAP5):​c.43+74T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.445 in 1,519,160 control chromosomes in the GnomAD database, including 156,318 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 0.53 (23528 hom., cov: 31)
  • Exomes 𝑓: 0.44 (132790 hom.)
• Consequence: GIMAP5 NM_018384.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0720
• Publications: 9 publications found

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]

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.78 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018384.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GIMAP5	NM_018384.5	MANE Select	c.43+74T>C		intron	N/A	NP_060854.2
	GIMAP1-GIMAP5	NM_001199577.2		c.655+74T>C		intron	N/A	NP_001186506.1
	GIMAP1-GIMAP5	NM_001303630.2		c.271+74T>C		intron	N/A	NP_001290559.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GIMAP5	ENST00000358647.5	TSL:1 MANE Select	c.43+74T>C		intron	N/A	ENSP00000351473.3
	GIMAP1-GIMAP5	ENST00000611999.4	TSL:5	c.655+74T>C		intron	N/A	ENSP00000477920.1
	GIMAP5	ENST00000476324.1	TSL:1	n.3318+74T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.532 AC: 80803 AN: 151798 Hom.: 23485 Cov.: 31

Gnomad AFR AF: 0.787

Gnomad AMI AF: 0.281

Gnomad AMR AF: 0.433

Gnomad ASJ AF: 0.397

Gnomad EAS AF: 0.376

Gnomad SAS AF: 0.496

Gnomad FIN AF: 0.555

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.423

Gnomad OTH AF: 0.489

GnomAD4 exome AF: 0.435 AC: 595336 AN: 1367244 Hom.: 132790 AF XY: 0.436 AC XY: 298304 AN XY: 684400

African (AFR) AF: 0.798 AC: 25075 AN: 31418

American (AMR) AF: 0.442 AC: 18833 AN: 42618

Ashkenazi Jewish (ASJ) AF: 0.382 AC: 9643 AN: 25246

East Asian (EAS) AF: 0.365 AC: 14284 AN: 39142

South Asian (SAS) AF: 0.479 AC: 39696 AN: 82860

European-Finnish (FIN) AF: 0.541 AC: 28690 AN: 53022

Middle Eastern (MID) AF: 0.422 AC: 2364 AN: 5602

European-Non Finnish (NFE) AF: 0.419 AC: 431511 AN: 1030092

Other (OTH) AF: 0.441 AC: 25240 AN: 57244

GnomAD4 genome AF: 0.533 AC: 80918 AN: 151916 Hom.: 23528 Cov.: 31 AF XY: 0.537 AC XY: 39833 AN XY: 74216

African (AFR) AF: 0.787 AC: 32571 AN: 41404

American (AMR) AF: 0.433 AC: 6616 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.397 AC: 1380 AN: 3472

East Asian (EAS) AF: 0.377 AC: 1944 AN: 5160

South Asian (SAS) AF: 0.496 AC: 2391 AN: 4816

European-Finnish (FIN) AF: 0.555 AC: 5845 AN: 10532

Middle Eastern (MID) AF: 0.480 AC: 141 AN: 294

European-Non Finnish (NFE) AF: 0.423 AC: 28740 AN: 67942

Other (OTH) AF: 0.489 AC: 1034 AN: 2116

Alfa AF: 0.502 Hom.: 3397

Bravo AF: 0.532

Asia WGS AF: 0.463 AC: 1610 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.2
DANN	Benign	0.44
PhyloP100		-0.072
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: rs4725936; hg19: chr7-150438089; COSMIC: COSV62281487; COSMIC: COSV62281487;