5-150898347-A-G

Variant names:

• chr5-150898347-A-G
• rs11741861
• NM_052860.4:c.142+81T>C

Variant summary

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

The NM_052860.4(ZNF300):​c.142+81T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0908 in 1,609,248 control chromosomes in the GnomAD database, including 9,208 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 0.093 (958 hom., cov: 32)
  • Exomes 𝑓: 0.091 (8250 hom.)
• Consequence: ZNF300 NM_052860.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0650
• Publications: 63 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.379 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF300	NM_052860.4	MANE Select	c.142+81T>C		intron	N/A	NP_443092.1
	ZNF300	NM_001172831.3		c.190+81T>C		intron	N/A	NP_001166302.1
	ZNF300	NM_001172832.3		c.34+81T>C		intron	N/A	NP_001166303.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF300	ENST00000274599.10	TSL:1 MANE Select	c.142+81T>C		intron	N/A	ENSP00000274599.5
	ZNF300	ENST00000446148.7	TSL:1	c.142+81T>C		intron	N/A	ENSP00000397178.3
	IRGM	ENST00000520549.1	TSL:1	n.*141-2242A>G		intron	N/A	ENSP00000429819.1

Frequencies

GnomAD3 genomes AF: 0.0929 AC: 14128 AN: 152084 Hom.: 959 Cov.: 32

Gnomad AFR AF: 0.0698

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.392

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.0810

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.0762

Gnomad OTH AF: 0.125

GnomAD4 exome AF: 0.0906 AC: 132051 AN: 1457046 Hom.: 8250 Cov.: 30 AF XY: 0.0920 AC XY: 66656 AN XY: 724820

African (AFR) AF: 0.0728 AC: 2429 AN: 33380

American (AMR) AF: 0.113 AC: 5043 AN: 44502

Ashkenazi Jewish (ASJ) AF: 0.167 AC: 4348 AN: 25960

East Asian (EAS) AF: 0.361 AC: 14290 AN: 39624

South Asian (SAS) AF: 0.131 AC: 11313 AN: 86106

European-Finnish (FIN) AF: 0.0818 AC: 4360 AN: 53286

Middle Eastern (MID) AF: 0.212 AC: 1218 AN: 5748

European-Non Finnish (NFE) AF: 0.0742 AC: 82232 AN: 1108254

Other (OTH) AF: 0.113 AC: 6818 AN: 60186

GnomAD4 genome AF: 0.0928 AC: 14124 AN: 152202 Hom.: 958 Cov.: 32 AF XY: 0.0956 AC XY: 7112 AN XY: 74406

African (AFR) AF: 0.0697 AC: 2896 AN: 41546

American (AMR) AF: 0.107 AC: 1640 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.161 AC: 558 AN: 3466

East Asian (EAS) AF: 0.393 AC: 2026 AN: 5152

South Asian (SAS) AF: 0.128 AC: 618 AN: 4822

European-Finnish (FIN) AF: 0.0810 AC: 859 AN: 10604

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.0762 AC: 5180 AN: 68000

Other (OTH) AF: 0.124 AC: 262 AN: 2110

Alfa AF: 0.0849 Hom.: 1228

Bravo AF: 0.0967

Asia WGS AF: 0.215 AC: 747 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	9.1
DANN	Benign	0.44
PhyloP100		0.065
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: rs11741861; hg19: chr5-150277909; COSMIC: COSV51032728;