rs1327866

Variant names:

• chr1-166983673-A-G
• rs1327866
• ENST00000622874.4:c.-120-5728A>G

Variant summary

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

The ENST00000622874.4(MAEL):​c.-120-5728A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 152,026 control chromosomes in the GnomAD database, including 5,588 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 0.26 (5588 hom., cov: 31)
• Consequence: MAEL ENST00000622874.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.534
• Publications: 4 publications found

Genes affected

MAEL (HGNC:25929): (maelstrom spermatogenic transposon silencer) Predicted to enable sequence-specific DNA binding activity. Predicted to be involved in gamete generation; negative regulation of macromolecule metabolic process; and piRNA metabolic process. Predicted to act upstream of or within several processes, including homologous chromosome pairing at meiosis; intrinsic apoptotic signaling pathway in response to DNA damage; and negative regulation of macromolecule metabolic process. Predicted to be located in piP-body. Predicted to be active in P granule and nucleus. [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=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.36 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAEL	NM_001286378.2	c.-120-5728A>G		intron_variant	Intron 1 of 12		NP_001273307.1
MAEL	XM_011510068.2	c.-120-5728A>G		intron_variant	Intron 1 of 12		XP_011508370.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAEL	ENST00000622874.4	c.-120-5728A>G		intron_variant	Intron 1 of 12	1		ENSP00000482771.1

Frequencies

GnomAD3 genomes AF: 0.262 AC: 39752 AN: 151908 Hom.: 5582 Cov.: 31

Gnomad AFR AF: 0.365

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.235

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.243

Gnomad OTH AF: 0.232

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

GnomAD4 genome AF: 0.262 AC: 39781 AN: 152026 Hom.: 5588 Cov.: 31 AF XY: 0.257 AC XY: 19077 AN XY: 74332

African (AFR) AF: 0.365 AC: 15122 AN: 41410

American (AMR) AF: 0.176 AC: 2696 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.172 AC: 598 AN: 3470

East Asian (EAS) AF: 0.236 AC: 1220 AN: 5174

South Asian (SAS) AF: 0.194 AC: 934 AN: 4818

European-Finnish (FIN) AF: 0.197 AC: 2083 AN: 10580

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.243 AC: 16500 AN: 67982

Other (OTH) AF: 0.229 AC: 484 AN: 2110

Alfa AF: 0.242 Hom.: 996

Bravo AF: 0.266

Asia WGS AF: 0.177 AC: 618 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.7
DANN	Benign	0.73
PhyloP100		0.53

Splicing

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

Other links and lift over

dbSNP: rs1327866; hg19: chr1-166952910;