22-30185733-C-T

Variant names:

• chr22-30185733-C-T
• rs5753037
• XM_011529914.3:c.820-21252C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000432360.3(ENSG00000225676):​n.307-952G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.298 in 151,954 control chromosomes in the GnomAD database, including 7,782 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 0.30 (7782 hom., cov: 32)
• Consequence: ENSG00000225676 ENST00000432360.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0680
• Publications: 74 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.25).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.559 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.246-952G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000225676	ENST00000432360.3	TSL:3	n.307-952G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.298 AC: 45273 AN: 151838 Hom.: 7793 Cov.: 32

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.318

Gnomad AMR AF: 0.288

Gnomad ASJ AF: 0.376

Gnomad EAS AF: 0.577

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.307

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.377

Gnomad OTH AF: 0.322

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

GnomAD4 genome AF: 0.298 AC: 45250 AN: 151954 Hom.: 7782 Cov.: 32 AF XY: 0.291 AC XY: 21568 AN XY: 74242

African (AFR) AF: 0.146 AC: 6054 AN: 41444

American (AMR) AF: 0.287 AC: 4386 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.376 AC: 1307 AN: 3472

East Asian (EAS) AF: 0.576 AC: 2978 AN: 5166

South Asian (SAS) AF: 0.132 AC: 638 AN: 4820

European-Finnish (FIN) AF: 0.307 AC: 3225 AN: 10520

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.377 AC: 25641 AN: 67950

Other (OTH) AF: 0.317 AC: 667 AN: 2106

Alfa AF: 0.364 Hom.: 38164

Bravo AF: 0.300

Asia WGS AF: 0.312 AC: 1085 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.25
CADD	Benign	18
DANN	Benign	0.61
PhyloP100		0.068

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: rs5753037;

hg19: chr22-30581722;