rs2271904

Positions:

• chr10-73134617-T-C
• chr10-73134617-T-G

Variant summary

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

The NM_007265.3(ECD):​c.1901A>G​(p.Asp634Gly) variant causes a missense change. The variant allele was found at a frequency of 0.083 in 1,614,064 control chromosomes in the GnomAD database, including 8,384 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.10 (1238 hom., cov: 32)
  • Exomes 𝑓: 0.081 (7146 hom.)
• Consequence: ECD NM_007265.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.68

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=0.0017505586).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ECD	NM_007265.3	c.1901A>G	p.Asp634Gly	missense_variant	14/14	ENST00000372979.9
ECD	NM_001135752.1	c.2000A>G	p.Asp667Gly	missense_variant	15/15
ECD	NM_001135753.1	c.1772A>G	p.Asp591Gly	missense_variant	13/13
ECD	NR_024203.1	n.1733A>G		non_coding_transcript_exon_variant	12/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ECD	ENST00000372979.9	c.1901A>G	p.Asp634Gly	missense_variant	14/14	1	NM_007265.3	P1

Frequencies

GnomAD3 genomes AF: 0.105 AC: 15923 AN: 152140 Hom.: 1218 Cov.: 32

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.0882

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.303

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.0411

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0607

Gnomad OTH AF: 0.0938

GnomAD3 exomes AF: 0.110 AC: 27648 AN: 251416 Hom.: 2389 AF XY: 0.113 AC XY: 15338 AN XY: 135878

Gnomad AFR exome AF: 0.161

Gnomad AMR exome AF: 0.0857

Gnomad ASJ exome AF: 0.113

Gnomad EAS exome AF: 0.306

Gnomad SAS exome AF: 0.226

Gnomad FIN exome AF: 0.0437

Gnomad NFE exome AF: 0.0609

Gnomad OTH exome AF: 0.0851

GnomAD4 exome AF: 0.0807 AC: 117965 AN: 1461806 Hom.: 7146 Cov.: 31 AF XY: 0.0846 AC XY: 61522 AN XY: 727208

Gnomad4 AFR exome AF: 0.165

Gnomad4 AMR exome AF: 0.0867

Gnomad4 ASJ exome AF: 0.111

Gnomad4 EAS exome AF: 0.280

Gnomad4 SAS exome AF: 0.222

Gnomad4 FIN exome AF: 0.0451

Gnomad4 NFE exome AF: 0.0602

Gnomad4 OTH exome AF: 0.0934

GnomAD4 genome AF: 0.105 AC: 15983 AN: 152258 Hom.: 1238 Cov.: 32 AF XY: 0.107 AC XY: 7985 AN XY: 74454

Gnomad4 AFR AF: 0.161

Gnomad4 AMR AF: 0.0882

Gnomad4 ASJ AF: 0.112

Gnomad4 EAS AF: 0.304

Gnomad4 SAS AF: 0.230

Gnomad4 FIN AF: 0.0411

Gnomad4 NFE AF: 0.0608

Gnomad4 OTH AF: 0.0961

Alfa AF: 0.0769 Hom.: 1549

Bravo AF: 0.108

TwinsUK AF: 0.0550 AC: 204

ALSPAC AF: 0.0579 AC: 223

ESP6500AA AF: 0.151 AC: 665

ESP6500EA AF: 0.0664 AC: 571

ExAC AF: 0.114 AC: 13818

Asia WGS AF: 0.259 AC: 898 AN: 3478

EpiCase AF: 0.0610

EpiControl AF: 0.0600

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.40
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.34	T;.;.
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.85	T;T;T
MetaRNN	Benign	0.0018	T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.9e-7	P;P;P
PrimateAI	Benign	0.41	T
PROVEAN	Pathogenic	-4.4	D;D;D
REVEL	Benign	0.19
Sift	Uncertain	0.0040	D;D;D
Sift4G	Uncertain	0.0070	D;D;D
Polyphen		0.99	D;.;.
Vest4		0.27
MPC		0.47
ClinPred		0.011	T
GERP RS		5.7
Varity_R		0.55
gMVP		0.47

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: rs2271904; hg19: chr10-74894375; COSMIC: COSV61968330; COSMIC: COSV61968330;