22-30196498-C-G

Variant names:

• chr22-30196498-C-G
• rs713875
• XM_011529914.3:c.820-10487C>G

Variant summary

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

The ENST00000432360.3(ENSG00000225676):​n.209-4268G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.472 in 151,984 control chromosomes in the GnomAD database, including 17,433 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 0.47 (17433 hom., cov: 32)
• Consequence: ENSG00000225676 ENST00000432360.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.514
• Publications: 69 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=-0.54).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.669 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.148-4268G>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000225676	ENST00000432360.3	TSL:3	n.209-4268G>C		intron	N/A
	ENSG00000225676	ENST00000760101.1		n.148-4268G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.472 AC: 71720 AN: 151866 Hom.: 17444 Cov.: 32

Gnomad AFR AF: 0.371

Gnomad AMI AF: 0.443

Gnomad AMR AF: 0.409

Gnomad ASJ AF: 0.478

Gnomad EAS AF: 0.688

Gnomad SAS AF: 0.393

Gnomad FIN AF: 0.462

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.539

Gnomad OTH AF: 0.467

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

GnomAD4 genome AF: 0.472 AC: 71720 AN: 151984 Hom.: 17433 Cov.: 32 AF XY: 0.465 AC XY: 34571 AN XY: 74284

African (AFR) AF: 0.371 AC: 15350 AN: 41410

American (AMR) AF: 0.409 AC: 6246 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.478 AC: 1659 AN: 3468

East Asian (EAS) AF: 0.688 AC: 3554 AN: 5166

South Asian (SAS) AF: 0.393 AC: 1895 AN: 4816

European-Finnish (FIN) AF: 0.462 AC: 4880 AN: 10568

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.539 AC: 36645 AN: 67978

Other (OTH) AF: 0.461 AC: 970 AN: 2106

Alfa AF: 0.530 Hom.: 11989

Bravo AF: 0.471

Asia WGS AF: 0.498 AC: 1731 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	16
DANN	Benign	0.66
PhyloP100		0.51

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: rs713875;

hg19: chr22-30592487;