5-150899025-C-T

Position:

• chr5-150899025-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_052860.4(ZNF300):​c.16-471G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.317 in 151,756 control chromosomes in the GnomAD database, including 12,756 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 0.32 (12756 hom., cov: 31)
• Consequence: ZNF300 NM_052860.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.522

Genes affected

ZNF300 (HGNC:13091): (zinc finger protein 300) The protein encoded by this gene is a C2H2-type zinc finger DNA binding protein and likely transcriptional regulator. The function of this protein is not yet known. Three transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Mar 2010]

IRGM (HGNC:29597): (immunity related GTPase M) This gene encodes a member of the p47 immunity-related GTPase family. The encoded protein may play a role in the innate immune response by regulating autophagy formation in response to intracellular pathogens. Polymorphisms that affect the normal expression of this gene are associated with a susceptibility to Crohn's disease and tuberculosis. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Oct 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.7 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF300	NM_052860.4	c.16-471G>A		intron_variant		ENST00000274599.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF300	ENST00000274599.10	c.16-471G>A		intron_variant		1	NM_052860.4	P1
ZNF300	ENST00000446148.7	c.16-471G>A		intron_variant		1		P1
IRGM	ENST00000520549.1	c.*141-1564C>T		intron_variant, NMD_transcript_variant		1
ZNF300	ENST00000427179.5	c.16-471G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.317 AC: 48080 AN: 151638 Hom.: 12711 Cov.: 31

Gnomad AFR AF: 0.706

Gnomad AMI AF: 0.161

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.205

Gnomad EAS AF: 0.594

Gnomad SAS AF: 0.274

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.300

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

GnomAD4 genome AF: 0.317 AC: 48176 AN: 151756 Hom.: 12756 Cov.: 31 AF XY: 0.317 AC XY: 23508 AN XY: 74186

Gnomad4 AFR AF: 0.707

Gnomad4 AMR AF: 0.215

Gnomad4 ASJ AF: 0.205

Gnomad4 EAS AF: 0.594

Gnomad4 SAS AF: 0.273

Gnomad4 FIN AF: 0.115

Gnomad4 NFE AF: 0.126

Gnomad4 OTH AF: 0.301

Alfa AF: 0.174 Hom.: 3404

Bravo AF: 0.346

Asia WGS AF: 0.421 AC: 1464 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.4
DANN	Benign	0.23

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: rs4958427; hg19: chr5-150278587;