rs10457678

Positions:

• chr6-138801103-A-G

Variant summary

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

The NM_001077706.3(ECT2L):​c.-244+4911A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 152,162 control chromosomes in the GnomAD database, including 3,209 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 0.19 (3209 hom., cov: 32)
• Consequence: ECT2L NM_001077706.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.82

Genes affected

ECT2L (HGNC:21118): (epithelial cell transforming 2 like) Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be involved in regulation of catalytic activity. [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=-0.99).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.25 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ECT2L	NM_001077706.3	c.-244+4911A>G		intron_variant		ENST00000541398.7	NP_001071174.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ECT2L	ENST00000541398.7	c.-244+4911A>G		intron_variant		5	NM_001077706.3	ENSP00000442307	P1
ECT2L	ENST00000367682.6	c.-104+4911A>G		intron_variant		5		ENSP00000356655	P1
ECT2L	ENST00000401414.4	c.-104+5120A>G		intron_variant		4		ENSP00000385187

Frequencies

GnomAD3 genomes AF: 0.188 AC: 28642 AN: 152044 Hom.: 3212 Cov.: 32

Gnomad AFR AF: 0.0638

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.257

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.184

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.255

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.239

Gnomad OTH AF: 0.218

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

GnomAD4 genome AF: 0.188 AC: 28632 AN: 152162 Hom.: 3209 Cov.: 32 AF XY: 0.188 AC XY: 13963 AN XY: 74390

Gnomad4 AFR AF: 0.0636

Gnomad4 AMR AF: 0.257

Gnomad4 ASJ AF: 0.269

Gnomad4 EAS AF: 0.184

Gnomad4 SAS AF: 0.110

Gnomad4 FIN AF: 0.255

Gnomad4 NFE AF: 0.239

Gnomad4 OTH AF: 0.215

Alfa AF: 0.234 Hom.: 8001

Bravo AF: 0.186

Asia WGS AF: 0.135 AC: 470 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.61
DANN	Benign	0.53

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: rs10457678; hg19: chr6-139122240;