rs17377643

Positions:

• chr22-41756984-A-C

Variant summary

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

The NM_152513.4(MEI1):​c.1952-1381A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.334 in 152,198 control chromosomes in the GnomAD database, including 9,626 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 0.33 (9626 hom., cov: 33)
• Consequence: MEI1 NM_152513.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.32

Genes affected

MEI1 (HGNC:28613): (meiotic double-stranded break formation protein 1) Predicted to be involved in meiosis I. Predicted to act upstream of or within gamete generation; meiotic spindle organization; and meiotic telomere clustering. Implicated in gestational trophoblastic neoplasm. [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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.435 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MEI1	NM_152513.4	c.1952-1381A>C		intron_variant		ENST00000401548.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MEI1	ENST00000401548.8	c.1952-1381A>C		intron_variant		1	NM_152513.4	P1

Frequencies

GnomAD3 genomes AF: 0.334 AC: 50814 AN: 152080 Hom.: 9627 Cov.: 33

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.397

Gnomad AMR AF: 0.270

Gnomad ASJ AF: 0.411

Gnomad EAS AF: 0.155

Gnomad SAS AF: 0.366

Gnomad FIN AF: 0.397

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.439

Gnomad OTH AF: 0.325

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

GnomAD4 genome AF: 0.334 AC: 50804 AN: 152198 Hom.: 9626 Cov.: 33 AF XY: 0.330 AC XY: 24576 AN XY: 74412

Gnomad4 AFR AF: 0.179

Gnomad4 AMR AF: 0.270

Gnomad4 ASJ AF: 0.411

Gnomad4 EAS AF: 0.155

Gnomad4 SAS AF: 0.366

Gnomad4 FIN AF: 0.397

Gnomad4 NFE AF: 0.440

Gnomad4 OTH AF: 0.322

Alfa AF: 0.418 Hom.: 24530

Bravo AF: 0.312

Asia WGS AF: 0.250 AC: 873 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.9
DANN	Benign	0.67

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

Publications

LitVar

Other links and lift over

dbSNP: rs17377643; hg19: chr22-42152988;