NM_152510.4:c.819+4256T>G

Variant names:

• chr22-30126470-T-G
• rs8135823
• NM_152510.4:c.819+4256T>G

Variant summary

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

The NM_152510.4(HORMAD2):​c.819+4256T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 152,030 control chromosomes in the GnomAD database, including 3,807 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 0.21 (3807 hom., cov: 32)
• Consequence: HORMAD2 NM_152510.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.702
• Publications: 4 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.259 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HORMAD2	NM_152510.4	c.819+4256T>G		intron_variant	Intron 10 of 10	ENST00000336726.11	NP_689723.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HORMAD2	ENST00000336726.11	c.819+4256T>G		intron_variant	Intron 10 of 10	1	NM_152510.4	ENSP00000336984.6
HORMAD2	ENST00000403975.1	c.819+4256T>G		intron_variant	Intron 10 of 10	2		ENSP00000385055.1

Frequencies

GnomAD3 genomes AF: 0.208 AC: 31617 AN: 151912 Hom.: 3811 Cov.: 32

Gnomad AFR AF: 0.0935

Gnomad AMI AF: 0.259

Gnomad AMR AF: 0.266

Gnomad ASJ AF: 0.311

Gnomad EAS AF: 0.0646

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.301

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.254

Gnomad OTH AF: 0.247

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

GnomAD4 genome AF: 0.208 AC: 31620 AN: 152030 Hom.: 3807 Cov.: 32 AF XY: 0.211 AC XY: 15664 AN XY: 74318

African (AFR) AF: 0.0934 AC: 3873 AN: 41482

American (AMR) AF: 0.266 AC: 4062 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.311 AC: 1080 AN: 3468

East Asian (EAS) AF: 0.0650 AC: 336 AN: 5170

South Asian (SAS) AF: 0.195 AC: 939 AN: 4816

European-Finnish (FIN) AF: 0.301 AC: 3177 AN: 10558

Middle Eastern (MID) AF: 0.381 AC: 112 AN: 294

European-Non Finnish (NFE) AF: 0.254 AC: 17288 AN: 67950

Other (OTH) AF: 0.245 AC: 517 AN: 2112

Alfa AF: 0.242 Hom.: 2060

Bravo AF: 0.201

Asia WGS AF: 0.108 AC: 377 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.8
DANN	Benign	0.81
PhyloP100		0.70
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: rs8135823; hg19: chr22-30522459;