rs17377643

Variant names:

• chr22-41756984-A-C
• rs17377643
• NM_152513.4:c.1952-1381A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 16 publications found

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]

MEI1 Gene-Disease associations (from GenCC):

• hydatidiform mole, recurrent, 3

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• complete hydatidiform mole

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152513.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEI1	NM_152513.4	MANE Select	c.1952-1381A>C		intron	N/A	NP_689726.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEI1	ENST00000401548.8	TSL:1 MANE Select	c.1952-1381A>C		intron	N/A	ENSP00000384115.3	Q5TIA1-1
	MEI1	ENST00000890163.1		c.1835-1381A>C		intron	N/A	ENSP00000560222.1
	MEI1	ENST00000540833.1	TSL:5	c.1172-1381A>C		intron	N/A	ENSP00000444225.1	F5GZT0

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

African (AFR) AF: 0.179 AC: 7433 AN: 41528

American (AMR) AF: 0.270 AC: 4126 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.411 AC: 1426 AN: 3470

East Asian (EAS) AF: 0.155 AC: 801 AN: 5172

South Asian (SAS) AF: 0.366 AC: 1767 AN: 4824

European-Finnish (FIN) AF: 0.397 AC: 4206 AN: 10596

Middle Eastern (MID) AF: 0.408 AC: 120 AN: 294

European-Non Finnish (NFE) AF: 0.440 AC: 29882 AN: 67988

Other (OTH) AF: 0.322 AC: 681 AN: 2116

Alfa AF: 0.403 Hom.: 52185

Bravo AF: 0.312

Asia WGS AF: 0.250 AC: 873 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.9
DANN	Benign	0.67
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17377643; hg19: chr22-42152988;