rs3812619

chr10-73163804-C-T

Variant summary

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

The NM_007265.3(ECD):c.134G>A(p.Arg45Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.096 in 1,613,782 control chromosomes in the GnomAD database, including 12,414 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.16 (3139 hom., cov: 32)
  • Exomes 𝑓: 0.090 (9275 hom.)
• Consequence: ECD NM_007265.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.12

Genes affected

ECD (HGNC:17029): (ecdysoneless cell cycle regulator) Enables histone acetyltransferase binding activity. Involved in positive regulation of transcription by RNA polymerase II. Located in cytosol and nucleoplasm. [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 (MetaRNN=0.0035088956).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.331 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ECD	NM_007265.3	c.134G>A	p.Arg45Gln	missense_variant	2/14	ENST00000372979.9
ECD	NM_001135752.1	c.134G>A	p.Arg45Gln	missense_variant	2/15
ECD	NM_001135753.1	c.134G>A	p.Arg45Gln	missense_variant	2/13
ECD	NR_024203.1	n.231-3253G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ECD	ENST00000372979.9	c.134G>A	p.Arg45Gln	missense_variant	2/14	1	NM_007265.3	P1

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23873 AN: 151888 Hom.: 3114 Cov.: 32

Gnomad AFR AF: 0.335

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.305

Gnomad SAS AF: 0.233

Gnomad FIN AF: 0.0423

Gnomad MID AF: 0.0764

Gnomad NFE AF: 0.0653

Gnomad OTH AF: 0.126

GnomAD3 exomes AF: 0.126 AC: 31788 AN: 251458 Hom.: 3257 AF XY: 0.126 AC XY: 17109 AN XY: 135896

Gnomad AFR exome AF: 0.343

Gnomad AMR exome AF: 0.0945

Gnomad ASJ exome AF: 0.129

Gnomad EAS exome AF: 0.306

Gnomad SAS exome AF: 0.227

Gnomad FIN exome AF: 0.0459

Gnomad NFE exome AF: 0.0658

Gnomad OTH exome AF: 0.0938

GnomAD4 exome AF: 0.0896 AC: 131028 AN: 1461774 Hom.: 9275 Cov.: 32 AF XY: 0.0927 AC XY: 67407 AN XY: 727194

Gnomad4 AFR exome AF: 0.346

Gnomad4 AMR exome AF: 0.0959

Gnomad4 ASJ exome AF: 0.124

Gnomad4 EAS exome AF: 0.281

Gnomad4 SAS exome AF: 0.224

Gnomad4 FIN exome AF: 0.0472

Gnomad4 NFE exome AF: 0.0645

Gnomad4 OTH exome AF: 0.110

GnomAD4 genome AF: 0.158 AC: 23950 AN: 152008 Hom.: 3139 Cov.: 32 AF XY: 0.158 AC XY: 11745 AN XY: 74308

Gnomad4 AFR AF: 0.336

Gnomad4 AMR AF: 0.106

Gnomad4 ASJ AF: 0.127

Gnomad4 EAS AF: 0.306

Gnomad4 SAS AF: 0.232

Gnomad4 FIN AF: 0.0423

Gnomad4 NFE AF: 0.0654

Gnomad4 OTH AF: 0.128

Alfa AF: 0.0911 Hom.: 2543

Bravo AF: 0.168

TwinsUK AF: 0.0583 AC: 216

ALSPAC AF: 0.0615 AC: 237

ESP6500AA AF: 0.325 AC: 1433

ESP6500EA AF: 0.0717 AC: 617

ExAC AF: 0.134 AC: 16203

Asia WGS AF: 0.270 AC: 937 AN: 3478

EpiCase AF: 0.0657

EpiControl AF: 0.0653

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.70
Cadd	Benign	13
Dann	Benign	0.56
DEOGEN2	Benign	0.018	T;.;.;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-0.98
FATHMM_MKL	Benign	0.038	N
LIST_S2	Benign	0.21	T;T;T;T
MetaRNN	Benign	0.0035	T;T;T;T
MetaSVM	Benign	-0.89	T
MutationTaster	Benign	0.90	P;P;P
PrimateAI	Benign	0.23	T
PROVEAN	Benign	0.57	N;N;N;N
REVEL	Benign	0.029
Sift	Benign	0.98	T;T;T;T
Sift4G	Benign	0.59	T;T;T;T
Polyphen		0.0	B;.;.;.
Vest4		0.052
MPC		0.092
ClinPred		0.0023	T
GERP RS		3.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.014
gMVP		0.19

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: rs3812619; hg19: chr10-74923562; COSMIC: COSV54351356; COSMIC: COSV54351356;