1-166980742-G-C

Position:

• chr1-166980742-G-C

Variant summary

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

The ENST00000622874.4(MAEL):​c.-121+5076G>C 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 151,984 control chromosomes in the GnomAD database, including 8,468 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 (8468 hom., cov: 31)
• Consequence: MAEL ENST00000622874.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.248

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=-0.78).
• 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/exons	MANE	UniProt
MAEL	NM_001286378.2	c.-121+5076G>C		intron_variant
MAEL	XM_011510068.2	c.-121+5076G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAEL	ENST00000622874.4	c.-121+5076G>C		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.307 AC: 46597 AN: 151866 Hom.: 8462 Cov.: 31

Gnomad AFR AF: 0.522

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.194

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.237

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: 46637 AN: 151984 Hom.: 8468 Cov.: 31 AF XY: 0.300 AC XY: 22275 AN XY: 74312

Gnomad4 AFR AF: 0.522

Gnomad4 AMR AF: 0.194

Gnomad4 ASJ AF: 0.172

Gnomad4 EAS AF: 0.237

Gnomad4 SAS AF: 0.194

Gnomad4 FIN AF: 0.197

Gnomad4 NFE AF: 0.243

Gnomad4 OTH AF: 0.267

Alfa AF: 0.121 Hom.: 185

Bravo AF: 0.317

Asia WGS AF: 0.186 AC: 650 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.3
DANN	Benign	0.70

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6682062; hg19: chr1-166949979;