chr6-138843073-T-C

Variant names:

• chr6-138843073-T-C
• rs76700722
• NM_001077706.3:c.437T>C

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.437T>C​(p.Ile146Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00216 in 1,613,916 control chromosomes in the GnomAD database, including 75 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

• Frequency:
  • Genomes: 𝑓 0.012 (39 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (36 hom.)
• Consequence: ECT2L NM_001077706.3 missense
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 6.10

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=0.0052326918).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0117 (1782/152292) while in subpopulation AFR AF = 0.0404 (1678/41572). AF 95% confidence interval is 0.0388. There are 39 homozygotes in GnomAd4. There are 849 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position FAILED quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
• BS2: High Homozygotes in GnomAd4 at 39 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ECT2L	NM_001077706.3	c.437T>C	p.Ile146Thr	missense_variant	Exon 6 of 22	ENST00000541398.7	NP_001071174.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ECT2L	ENST00000541398.7	c.437T>C	p.Ile146Thr	missense_variant	Exon 6 of 22	5	NM_001077706.3	ENSP00000442307.2
ECT2L	ENST00000367682.6	c.437T>C	p.Ile146Thr	missense_variant	Exon 5 of 21	5		ENSP00000356655.2

Frequencies

GnomAD3 genomes AF: 0.0116 AC: 1772 AN: 152174 Hom.: 39 Cov.: 32

Gnomad AFR AF: 0.0402

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00452

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.0110

GnomAD2 exomes AF: 0.00284 AC: 709 AN: 249492 AF XY: 0.00236

Gnomad AFR exome AF: 0.0409

Gnomad AMR exome AF: 0.00148

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000556

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000795

Gnomad OTH exome AF: 0.00182

GnomAD4 exome AF: 0.00117 AC: 1705 AN: 1461624 Hom.: 36 Cov.: 31 AF XY: 0.00104 AC XY: 753 AN XY: 727114

Gnomad4 AFR exome AF: 0.0421 AC: 1410 AN: 33478

Gnomad4 AMR exome AF: 0.00165 AC: 74 AN: 44716

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 26126

Gnomad4 EAS exome AF: 0.0000252 AC: 1 AN: 39698

Gnomad4 SAS exome AF: 0.000197 AC: 17 AN: 86184

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 53416

Gnomad4 NFE exome AF: 0.0000171 AC: 19 AN: 1111858

Gnomad4 Remaining exome AF: 0.00280 AC: 169 AN: 60380

GnomAD4 genome AF: 0.0117 AC: 1782 AN: 152292 Hom.: 39 Cov.: 32 AF XY: 0.0114 AC XY: 849 AN XY: 74476

Gnomad4 AFR AF: 0.0404 AC: 0.0403637 AN: 0.0403637

Gnomad4 AMR AF: 0.00451 AC: 0.00451216 AN: 0.00451216

Gnomad4 ASJ AF: 0.00 AC: 0 AN: 0

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.000207 AC: 0.000207211 AN: 0.000207211

Gnomad4 FIN AF: 0.00 AC: 0 AN: 0

Gnomad4 NFE AF: 0.000147 AC: 0.000147024 AN: 0.000147024

Gnomad4 OTH AF: 0.0109 AC: 0.0108696 AN: 0.0108696

Alfa AF: 0.00449 Hom.: 38

Bravo AF: 0.0138

ESP6500AA AF: 0.0353 AC: 140

ESP6500EA AF: 0.000120 AC: 1

ExAC AF: 0.00345 AC: 417

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.0000546

EpiControl AF: 0.000178

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

not specified Other:1

Sep 19, 2013

ITMI

Significance: not provided

Review Status: no classification provided

Collection Method: reference population

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.052	T;T;T
Eigen	Benign	-0.057
Eigen_PC	Benign	0.014
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.80	.;.;T
MetaRNN	Benign	0.0052	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.5	M;M;M
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-4.0	D;D;.
REVEL	Benign	0.18
Sift	Uncertain	0.0040	D;D;.
Sift4G	Uncertain	0.0040	D;D;D
Polyphen		0.36	B;B;B
Vest4		0.61
MVP		0.43
MPC		0.30
ClinPred		0.050	T
GERP RS		5.7
Varity_R		0.39
gMVP		0.39
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs76700722; hg19: chr6-139164210;