5-150899025-C-T

Variant names:

• chr5-150899025-C-T
• rs4958427
• NM_052860.4:c.16-471G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 14 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052860.4. 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
	ZNF300	NM_052860.4	MANE Select	c.16-471G>A		intron	N/A	NP_443092.1	Q96RE9-1
	ZNF300	NM_001172831.3		c.64-471G>A		intron	N/A	NP_001166302.1	Q96RE9-3
	ZNF300	NM_001172832.3		c.-93-471G>A		intron	N/A	NP_001166303.1	Q96RE9-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF300	ENST00000274599.10	TSL:1 MANE Select	c.16-471G>A		intron	N/A	ENSP00000274599.5	Q96RE9-1
	ZNF300	ENST00000446148.7	TSL:1	c.16-471G>A		intron	N/A	ENSP00000397178.3	Q96RE9-1
	IRGM	ENST00000520549.1	TSL:1	n.*141-1564C>T		intron	N/A	ENSP00000429819.1	A0A9H4B933

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

African (AFR) AF: 0.707 AC: 29213 AN: 41340

American (AMR) AF: 0.215 AC: 3274 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.205 AC: 710 AN: 3462

East Asian (EAS) AF: 0.594 AC: 3044 AN: 5122

South Asian (SAS) AF: 0.273 AC: 1313 AN: 4804

European-Finnish (FIN) AF: 0.115 AC: 1214 AN: 10552

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.126 AC: 8531 AN: 67930

Other (OTH) AF: 0.301 AC: 634 AN: 2106

Alfa AF: 0.198 Hom.: 6248

Bravo AF: 0.346

Asia WGS AF: 0.421 AC: 1464 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.4
DANN	Benign	0.23
PhyloP100		0.52
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: rs4958427; hg19: chr5-150278587;