rs11741861

Positions:

• chr5-150898347-A-G
• chr5-150898347-A-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF300	NM_052860.4	c.142+81T>C		intron_variant		ENST00000274599.10	NP_443092.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF300	ENST00000274599.10	c.142+81T>C		intron_variant		1	NM_052860.4	ENSP00000274599	P1
ZNF300	ENST00000446148.7	c.142+81T>C		intron_variant		1		ENSP00000397178	P1
IRGM	ENST00000520549.1	c.*141-2242A>G		intron_variant, NMD_transcript_variant		1		ENSP00000429819
ZNF300	ENST00000427179.5	c.142+81T>C		intron_variant		2		ENSP00000414195

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

Gnomad4 AFR exome AF: 0.0728

Gnomad4 AMR exome AF: 0.113

Gnomad4 ASJ exome AF: 0.167

Gnomad4 EAS exome AF: 0.361

Gnomad4 SAS exome AF: 0.131

Gnomad4 FIN exome AF: 0.0818

Gnomad4 NFE exome AF: 0.0742

Gnomad4 OTH exome AF: 0.113

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

Gnomad4 AFR AF: 0.0697

Gnomad4 AMR AF: 0.107

Gnomad4 ASJ AF: 0.161

Gnomad4 EAS AF: 0.393

Gnomad4 SAS AF: 0.128

Gnomad4 FIN AF: 0.0810

Gnomad4 NFE AF: 0.0762

Gnomad4 OTH AF: 0.124

Alfa AF: 0.0812 Hom.: 199

Bravo AF: 0.0967

Asia WGS AF: 0.215 AC: 747 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	9.1
DANN	Benign	0.44

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: rs11741861; hg19: chr5-150277909; COSMIC: COSV51032728;