NM_018326.3:c.-14-141G>C

Variant names:

• chr7-150569747-G-C
• rs11769703
• NM_018326.3:c.-14-141G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018326.3(GIMAP4):​c.-14-141G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000231 in 432,966 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0000023 (0 hom.)
• Consequence: GIMAP4 NM_018326.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0760
• Publications: 0 publications found

Genes affected

GIMAP4 (HGNC:21872): (GTPase, IMAP family member 4) This gene encodes a protein belonging to the GTP-binding superfamily and to the immuno-associated nucleotide (IAN) subfamily of nucleotide-binding proteins. The encoded protein of this gene may be negatively regulated by T-cell acute lymphocytic leukemia 1 (TAL1). In humans, the IAN subfamily genes are located in a cluster at 7q36.1. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GIMAP4	NM_018326.3	c.-14-141G>C		intron_variant	Intron 1 of 2	ENST00000255945.4	NP_060796.1
GIMAP4	NM_001363532.2	c.-14-141G>C		intron_variant	Intron 1 of 2		NP_001350461.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GIMAP4	ENST00000255945.4	c.-14-141G>C		intron_variant	Intron 1 of 2	1	NM_018326.3	ENSP00000255945.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000231 AC: 1 AN: 432966 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 227970

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 12052

American (AMR) AF: 0.00 AC: 0 AN: 17980

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13220

East Asian (EAS) AF: 0.00 AC: 0 AN: 29804

South Asian (SAS) AF: 0.00 AC: 0 AN: 41148

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32670

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3526

European-Non Finnish (NFE) AF: 0.00000389 AC: 1 AN: 257340

Other (OTH) AF: 0.00 AC: 0 AN: 25226

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.3
DANN	Benign	0.61
PhyloP100		-0.076

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: rs11769703; hg19: chr7-150266835;