7-150728263-G-T

Variant names:

• chr7-150728263-G-T
• rs6945478
• ENST00000611999.4:c.402+7857G>T

Variant summary

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

The NM_001199577.2(GIMAP1-GIMAP5):​c.402+7857G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 152,246 control chromosomes in the GnomAD database, including 994 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 0.11 (994 hom., cov: 32)
• Consequence: GIMAP1-GIMAP5 NM_001199577.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.507
• Publications: 5 publications found

Genes affected

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]

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 Gene-Disease associations (from GenCC):

• portal hypertension, noncirrhotic, 2

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001199577.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GIMAP1-GIMAP5	NM_001199577.2		c.402+7857G>T		intron	N/A	NP_001186506.1	A0A087WTJ2
	GIMAP1-GIMAP5	NM_001303630.2		c.18+9173G>T		intron	N/A	NP_001290559.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GIMAP1-GIMAP5	ENST00000611999.4	TSL:5	c.402+7857G>T		intron	N/A	ENSP00000477920.1	A0A087WTJ2
	GIMAP5	ENST00000498181.6	TSL:4	c.-211+5893G>T		intron	N/A	ENSP00000487840.2	Q96F15-1

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16431 AN: 152128 Hom.: 994 Cov.: 32

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.0802

Gnomad AMR AF: 0.0958

Gnomad ASJ AF: 0.0876

Gnomad EAS AF: 0.197

Gnomad SAS AF: 0.100

Gnomad FIN AF: 0.108

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0945

Gnomad OTH AF: 0.114

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.108 AC: 16460 AN: 152246 Hom.: 994 Cov.: 32 AF XY: 0.109 AC XY: 8112 AN XY: 74440

African (AFR) AF: 0.127 AC: 5271 AN: 41518

American (AMR) AF: 0.0956 AC: 1463 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0876 AC: 304 AN: 3472

East Asian (EAS) AF: 0.198 AC: 1025 AN: 5186

South Asian (SAS) AF: 0.101 AC: 487 AN: 4826

European-Finnish (FIN) AF: 0.108 AC: 1144 AN: 10610

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0945 AC: 6426 AN: 68012

Other (OTH) AF: 0.115 AC: 242 AN: 2112

Alfa AF: 0.0971 Hom.: 1020

Bravo AF: 0.109

Asia WGS AF: 0.156 AC: 543 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.4
DANN	Benign	0.79
PhyloP100		-0.51

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: rs6945478; hg19: chr7-150425351;