6-138801103-A-G

Variant names:

• chr6-138801103-A-G
• rs10457678
• NM_001077706.3:c.-244+4911A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001077706.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ECT2L	NM_001077706.3	MANE Select	c.-244+4911A>G		intron	N/A	NP_001071174.1
	ECT2L	NM_001195037.2		c.-104+4911A>G		intron	N/A	NP_001181966.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ECT2L	ENST00000541398.7	TSL:5 MANE Select	c.-244+4911A>G		intron	N/A	ENSP00000442307.2
	ECT2L	ENST00000367682.6	TSL:5	c.-104+4911A>G		intron	N/A	ENSP00000356655.2
	ECT2L	ENST00000401414.4	TSL:4	c.-104+5120A>G		intron	N/A	ENSP00000385187.3

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

African (AFR) AF: 0.0636 AC: 2644 AN: 41550

American (AMR) AF: 0.257 AC: 3926 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.269 AC: 935 AN: 3472

East Asian (EAS) AF: 0.184 AC: 952 AN: 5172

South Asian (SAS) AF: 0.110 AC: 530 AN: 4826

European-Finnish (FIN) AF: 0.255 AC: 2696 AN: 10566

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.239 AC: 16239 AN: 67984

Other (OTH) AF: 0.215 AC: 454 AN: 2112

Alfa AF: 0.224 Hom.: 11997

Bravo AF: 0.186

Asia WGS AF: 0.135 AC: 470 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.61
DANN	Benign	0.53
PhyloP100		-1.8
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: rs10457678; hg19: chr6-139122240;