22-30202563-C-G

Variant names:

• chr22-30202563-C-G
• rs17728461
• XM_011529914.3:c.820-4422C>G

Variant summary

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

The ENST00000432360.3(ENSG00000225676):​n.208+4485G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 151,996 control chromosomes in the GnomAD database, including 5,835 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 0.25 (5835 hom., cov: 31)
• Consequence: ENSG00000225676 ENST00000432360.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0960
• Publications: 23 publications found

Genes affected

HORMAD2 (HGNC:28383): (HORMA domain containing 2) Predicted to be involved in meiotic sister chromatid cohesion. Located in centrosome; cytosol; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000225676 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000432360.3. 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
	LOC105372988	NR_188588.1		n.147+4485G>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000225676	ENST00000432360.3	TSL:3	n.208+4485G>C		intron	N/A
	ENSG00000225676	ENST00000760101.1		n.147+4485G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.253 AC: 38371 AN: 151878 Hom.: 5829 Cov.: 31

Gnomad AFR AF: 0.0863

Gnomad AMI AF: 0.225

Gnomad AMR AF: 0.273

Gnomad ASJ AF: 0.288

Gnomad EAS AF: 0.181

Gnomad SAS AF: 0.318

Gnomad FIN AF: 0.437

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.273

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

GnomAD4 genome AF: 0.253 AC: 38394 AN: 151996 Hom.: 5835 Cov.: 31 AF XY: 0.260 AC XY: 19311 AN XY: 74268

African (AFR) AF: 0.0862 AC: 3576 AN: 41482

American (AMR) AF: 0.273 AC: 4172 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.288 AC: 1000 AN: 3470

East Asian (EAS) AF: 0.181 AC: 937 AN: 5168

South Asian (SAS) AF: 0.317 AC: 1528 AN: 4822

European-Finnish (FIN) AF: 0.437 AC: 4598 AN: 10532

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.319 AC: 21663 AN: 67940

Other (OTH) AF: 0.282 AC: 596 AN: 2110

Alfa AF: 0.296 Hom.: 949

Bravo AF: 0.232

Asia WGS AF: 0.239 AC: 833 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	12
DANN	Benign	0.70
PhyloP100		0.096

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs17728461;

hg19: chr22-30598552;