rs201270230

Variant names:

• chr6-138868138-A-G
• rs201270230
• NM_001077706.3:c.1510A>G

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BS1_Supporting BS2

The NM_001077706.3(ECT2L):​c.1510A>G​(p.Ile504Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00136 in 1,613,316 control chromosomes in the GnomAD database, including 54 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

• Frequency:
  • Genomes: 𝑓 0.00087 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0014 (52 hom.)
• Consequence: ECT2L NM_001077706.3 missense
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 0.283
• Publications: 2 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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0031599104).
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.000866 (132/152360) while in subpopulation SAS AF = 0.0263 (127/4830). AF 95% confidence interval is 0.0226. There are 2 homozygotes in GnomAd4. There are 96 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ECT2L	NM_001077706.3	MANE Select	c.1510A>G	p.Ile504Val	missense	Exon 13 of 22	NP_001071174.1
	ECT2L	NM_001195037.2		c.1510A>G	p.Ile504Val	missense	Exon 12 of 21	NP_001181966.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ECT2L	ENST00000541398.7	TSL:5 MANE Select	c.1510A>G	p.Ile504Val	missense	Exon 13 of 22	ENSP00000442307.2
	ECT2L	ENST00000367682.6	TSL:5	c.1510A>G	p.Ile504Val	missense	Exon 12 of 21	ENSP00000356655.2
	ECT2L	ENST00000495970.1	TSL:3	n.498A>G		non_coding_transcript_exon	Exon 5 of 6

Frequencies

GnomAD3 genomes AF: 0.000874 AC: 133 AN: 152242 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0265

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.00301 AC: 750 AN: 248946 AF XY: 0.00385

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000291

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000557

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000265

Gnomad OTH exome AF: 0.00248

GnomAD4 exome AF: 0.00141 AC: 2056 AN: 1460956 Hom.: 52 Cov.: 31 AF XY: 0.00200 AC XY: 1450 AN XY: 726738

African (AFR) AF: 0.00 AC: 0 AN: 33462

American (AMR) AF: 0.0000224 AC: 1 AN: 44662

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39676

South Asian (SAS) AF: 0.0221 AC: 1904 AN: 86034

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53400

Middle Eastern (MID) AF: 0.00208 AC: 12 AN: 5768

European-Non Finnish (NFE) AF: 0.0000333 AC: 37 AN: 1111484

Other (OTH) AF: 0.00167 AC: 101 AN: 60350

GnomAD4 genome AF: 0.000866 AC: 132 AN: 152360 Hom.: 2 Cov.: 32 AF XY: 0.00129 AC XY: 96 AN XY: 74510

African (AFR) AF: 0.00 AC: 0 AN: 41584

American (AMR) AF: 0.0000653 AC: 1 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000192 AC: 1 AN: 5196

South Asian (SAS) AF: 0.0263 AC: 127 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68032

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.000201 Hom.: 0

Bravo AF: 0.000174

ExAC AF: 0.00340 AC: 411

Asia WGS AF: 0.0150 AC: 53 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.00

ClinVar

ClinVar submissions as Germline

Significance: not provided

Revision: no classification provided

Pathogenic	VUS	Benign	Condition
-	-	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	4.1
DANN	Benign	0.24
DEOGEN2	Benign	0.0032	T
Eigen	Benign	-0.99
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.027	N
LIST_S2	Benign	0.47	T
MetaRNN	Benign	0.0032	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
PhyloP100		0.28
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.26	N
REVEL	Benign	0.049
Sift	Benign	0.52	T
Sift4G	Benign	0.48	T
Polyphen		0.0010	B
Vest4		0.15
MutPred		0.29		Gain of disorder (P = 0.1708)
MVP		0.20
MPC		0.073
ClinPred		0.013	T
GERP RS		3.4
Varity_R		0.025
gMVP		0.12
Mutation Taster		=99/1	polymorphism

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: rs201270230; hg19: chr6-139189275;