6-77815141-C-T

Position:

• chr6-77815141-C-T

Variant summary

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

The NM_001322247.2(MEI4):​c.769-13790C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.832 in 151,988 control chromosomes in the GnomAD database, including 53,051 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 0.83 (53051 hom., cov: 30)
• Consequence: MEI4 NM_001322247.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.650

Genes affected

MEI4 (HGNC:43638): (meiotic double-stranded break formation protein 4) Predicted to be involved in gamete generation and meiosis I cell cycle process. Predicted to be active in lateral element. [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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.93 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MEI4	NM_001322247.2	c.769-13790C>T		intron_variant		ENST00000684080.1	NP_001309176.1
MEI4	NM_001282136.3	c.769-13790C>T		intron_variant			NP_001269065.1
MEI4	XM_017010155.2	c.769-13796C>T		intron_variant			XP_016865644.1
MEI4	XM_005248774.5	c.475-13790C>T		intron_variant			XP_005248831.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MEI4	ENST00000684080.1	c.769-13790C>T		intron_variant			NM_001322247.2	ENSP00000507827.1
MEI4	ENST00000602452.3	c.769-13790C>T		intron_variant		5		ENSP00000473370.1
MEI4	ENST00000649759.1	c.769-13790C>T		intron_variant				ENSP00000496917.1

Frequencies

GnomAD3 genomes AF: 0.832 AC: 126285 AN: 151870 Hom.: 52997 Cov.: 30

Gnomad AFR AF: 0.938

Gnomad AMI AF: 0.705

Gnomad AMR AF: 0.843

Gnomad ASJ AF: 0.790

Gnomad EAS AF: 0.950

Gnomad SAS AF: 0.724

Gnomad FIN AF: 0.822

Gnomad MID AF: 0.666

Gnomad NFE AF: 0.769

Gnomad OTH AF: 0.806

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

GnomAD4 genome AF: 0.832 AC: 126396 AN: 151988 Hom.: 53051 Cov.: 30 AF XY: 0.833 AC XY: 61852 AN XY: 74296

Gnomad4 AFR AF: 0.938

Gnomad4 AMR AF: 0.843

Gnomad4 ASJ AF: 0.790

Gnomad4 EAS AF: 0.950

Gnomad4 SAS AF: 0.721

Gnomad4 FIN AF: 0.822

Gnomad4 NFE AF: 0.769

Gnomad4 OTH AF: 0.807

Alfa AF: 0.812 Hom.: 8523

Bravo AF: 0.840

Asia WGS AF: 0.871 AC: 3027 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.30
DANN	Benign	0.34

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: rs1398576; hg19: chr6-78524858;