rs7545911

Variant names:

• chr1-166978444-G-A
• rs7545911
• ENST00000622874.4:c.-121+2778G>A

Variant summary

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

The ENST00000622874.4(MAEL):​c.-121+2778G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 152,032 control chromosomes in the GnomAD database, including 8,477 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 0.31 (8477 hom., cov: 32)
• Consequence: MAEL ENST00000622874.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.311
• Publications: 7 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.516 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAEL	NM_001286378.2	c.-121+2778G>A		intron_variant	Intron 1 of 12		NP_001273307.1
MAEL	XM_011510068.2	c.-121+2778G>A		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.-121+2778G>A		intron_variant	Intron 1 of 12	1		ENSP00000482771.1

Frequencies

GnomAD3 genomes AF: 0.307 AC: 46608 AN: 151914 Hom.: 8469 Cov.: 32

Gnomad AFR AF: 0.522

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.194

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.236

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.243

Gnomad OTH AF: 0.270

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

GnomAD4 genome AF: 0.307 AC: 46652 AN: 152032 Hom.: 8477 Cov.: 32 AF XY: 0.300 AC XY: 22279 AN XY: 74332

African (AFR) AF: 0.522 AC: 21606 AN: 41406

American (AMR) AF: 0.194 AC: 2959 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.172 AC: 597 AN: 3468

East Asian (EAS) AF: 0.236 AC: 1220 AN: 5170

South Asian (SAS) AF: 0.194 AC: 934 AN: 4816

European-Finnish (FIN) AF: 0.197 AC: 2086 AN: 10592

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.243 AC: 16537 AN: 67978

Other (OTH) AF: 0.267 AC: 565 AN: 2114

Alfa AF: 0.263 Hom.: 13447

Bravo AF: 0.317

Asia WGS AF: 0.187 AC: 652 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.0
DANN	Benign	0.22
PhyloP100		0.31

Splicing

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

Other links and lift over

dbSNP: rs7545911; hg19: chr1-166947681;