rs7528849

Positions:

• chr1-166985633-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000622874.4(MAEL):​c.-120-3768A>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 152,124 control chromosomes in the GnomAD database, including 5,593 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 (5593 hom., cov: 32)
• Consequence: MAEL ENST00000622874.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.26

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.361 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAEL	NM_001286378.2	c.-120-3768A>G		intron_variant			NP_001273307.1
MAEL	XM_006711583.2	c.3+285A>G		intron_variant			XP_006711646.1
MAEL	XM_011510068.2	c.-120-3768A>G		intron_variant			XP_011508370.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAEL	ENST00000622874.4	c.-120-3768A>G		intron_variant		1		ENSP00000482771

Frequencies

GnomAD3 genomes AF: 0.262 AC: 39792 AN: 152006 Hom.: 5587 Cov.: 32

Gnomad AFR AF: 0.366

Gnomad AMI AF: 0.112

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: 0.233

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

GnomAD4 genome AF: 0.262 AC: 39821 AN: 152124 Hom.: 5593 Cov.: 32 AF XY: 0.257 AC XY: 19099 AN XY: 74386

Gnomad4 AFR AF: 0.365

Gnomad4 AMR AF: 0.176

Gnomad4 ASJ AF: 0.172

Gnomad4 EAS AF: 0.235

Gnomad4 SAS AF: 0.194

Gnomad4 FIN AF: 0.197

Gnomad4 NFE AF: 0.243

Gnomad4 OTH AF: 0.230

Alfa AF: 0.238 Hom.: 770

Bravo AF: 0.266

Asia WGS AF: 0.177 AC: 617 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	16
DANN	Benign	0.54

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7528849; hg19: chr1-166954870;