rs4459610

Variant names:

• chr17-63507359-A-T
• rs4459610
• ENST00000577647.2:n.2145A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000577647.2(ENSG00000264813):​n.2145A>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.54 in 398,798 control chromosomes in the GnomAD database, including 60,001 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 0.54 (22985 hom., cov: 32)
  • Exomes 𝑓: 0.54 (37016 hom.)
• Consequence: ENSG00000264813 ENST00000577647.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.117
• Publications: 19 publications found

Genes affected

ENSG00000264813 (HGNC:):

ACE3P (HGNC:44365): (angiotensin I converting enzyme 3, pseudogene) Predicted to be located in acrosomal vesicle. [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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.57 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000577647.2. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000264813	ENST00000577647.2	TSL:2	n.2145A>T		non_coding_transcript_exon	Exon 15 of 31	ENSP00000464149.1	F6X3S4
	ACE3P	ENST00000423435.2		n.58-205A>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.544 AC: 82666 AN: 151888 Hom.: 22965 Cov.: 32

Gnomad AFR AF: 0.575

Gnomad AMI AF: 0.698

Gnomad AMR AF: 0.473

Gnomad ASJ AF: 0.663

Gnomad EAS AF: 0.259

Gnomad SAS AF: 0.404

Gnomad FIN AF: 0.474

Gnomad MID AF: 0.734

Gnomad NFE AF: 0.574

Gnomad OTH AF: 0.580

GnomAD2 exomes AF: 0.552 AC: 4845 AN: 8782 AF XY: 0.559

Gnomad AFR exome AF: 0.535

Gnomad AMR exome AF: 0.424

Gnomad ASJ exome AF: 0.707

Gnomad EAS exome AF: 0.236

Gnomad FIN exome AF: 0.486

Gnomad NFE exome AF: 0.572

Gnomad OTH exome AF: 0.592

GnomAD4 exome AF: 0.537 AC: 132457 AN: 246792 Hom.: 37016 Cov.: 0 AF XY: 0.541 AC XY: 67622 AN XY: 125090

African (AFR) AF: 0.581 AC: 4175 AN: 7180

American (AMR) AF: 0.437 AC: 3252 AN: 7434

Ashkenazi Jewish (ASJ) AF: 0.680 AC: 6286 AN: 9240

East Asian (EAS) AF: 0.267 AC: 6109 AN: 22894

South Asian (SAS) AF: 0.404 AC: 1226 AN: 3032

European-Finnish (FIN) AF: 0.496 AC: 10542 AN: 21260

Middle Eastern (MID) AF: 0.685 AC: 887 AN: 1294

European-Non Finnish (NFE) AF: 0.576 AC: 91108 AN: 158074

Other (OTH) AF: 0.542 AC: 8872 AN: 16384

GnomAD4 genome AF: 0.544 AC: 82721 AN: 152006 Hom.: 22985 Cov.: 32 AF XY: 0.534 AC XY: 39639 AN XY: 74288

African (AFR) AF: 0.575 AC: 23831 AN: 41480

American (AMR) AF: 0.472 AC: 7212 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.663 AC: 2302 AN: 3470

East Asian (EAS) AF: 0.259 AC: 1334 AN: 5156

South Asian (SAS) AF: 0.405 AC: 1948 AN: 4814

European-Finnish (FIN) AF: 0.474 AC: 5007 AN: 10572

Middle Eastern (MID) AF: 0.738 AC: 217 AN: 294

European-Non Finnish (NFE) AF: 0.574 AC: 39024 AN: 67936

Other (OTH) AF: 0.576 AC: 1214 AN: 2106

Alfa AF: 0.566 Hom.: 3047

Bravo AF: 0.544

Asia WGS AF: 0.331 AC: 1157 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_noAF	Benign	-0.82
CADD	Benign	9.0
DANN	Benign	0.75
PhyloP100		-0.12
Mutation Taster		=98/2	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs4459610;

hg19: chr17-61584720;