1-3556364-T-C

Position:

• chr1-3556364-T-C

Variant summary

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

The NM_001409.4(MEGF6):​c.481+23461A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.284 in 152,158 control chromosomes in the GnomAD database, including 11,105 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 0.28 (11105 hom., cov: 33)
• Consequence: MEGF6 NM_001409.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.17

Genes affected

MEGF6 (HGNC:3232): (multiple EGF like domains 6) Predicted to enable calcium ion binding activity. Predicted to be located in extracellular region. [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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.686 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MEGF6	NM_001409.4	c.481+23461A>G		intron_variant		ENST00000356575.9	NP_001400.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MEGF6	ENST00000356575.9	c.481+23461A>G		intron_variant		1	NM_001409.4	ENSP00000348982	P1
MEGF6	ENST00000485002.6	c.377-9241A>G		intron_variant, NMD_transcript_variant		5		ENSP00000419033

Frequencies

GnomAD3 genomes AF: 0.284 AC: 43109 AN: 152040 Hom.: 11060 Cov.: 33

Gnomad AFR AF: 0.692

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.0429

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.233

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

GnomAD4 genome AF: 0.284 AC: 43212 AN: 152158 Hom.: 11105 Cov.: 33 AF XY: 0.280 AC XY: 20805 AN XY: 74404

Gnomad4 AFR AF: 0.692

Gnomad4 AMR AF: 0.142

Gnomad4 ASJ AF: 0.149

Gnomad4 EAS AF: 0.0430

Gnomad4 SAS AF: 0.231

Gnomad4 FIN AF: 0.115

Gnomad4 NFE AF: 0.126

Gnomad4 OTH AF: 0.236

Alfa AF: 0.134 Hom.: 2609

Bravo AF: 0.299

Asia WGS AF: 0.185 AC: 643 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	0.0080
DANN	Benign	0.20

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: rs878063; hg19: chr1-3472928;