rs28727473

Variant names:

• chr4-41749306-G-A
• rs28727473
• ENST00000819356.1:n.345G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The ENST00000819356.1(PHOX2B-AS1):​n.345G>A variant causes a non coding transcript exon change. The variant allele was found at a frequency of 0.0831 in 152,186 control chromosomes in the GnomAD database, including 579 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.083 (579 hom., cov: 32)
• Consequence: PHOX2B-AS1 ENST00000819356.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.08
• Publications: 1 publications found

Genes affected

PHOX2B-AS1 (HGNC:40457): (PHOX2B antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BP6: Variant 4-41749306-G-A is Benign according to our data. Variant chr4-41749306-G-A is described in ClinVar as Benign. ClinVar VariationId is 1271400.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0884 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000819356.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHOX2B-AS1	NR_187403.1		n.238+720G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHOX2B-AS1	ENST00000819356.1		n.345G>A		non_coding_transcript_exon	Exon 2 of 5
	PHOX2B-AS1	ENST00000819357.1		n.107G>A		non_coding_transcript_exon	Exon 1 of 4
	PHOX2B-AS1	ENST00000819359.1		n.177G>A		non_coding_transcript_exon	Exon 1 of 5

Frequencies

GnomAD3 genomes AF: 0.0832 AC: 12647 AN: 152068 Hom.: 581 Cov.: 32

Gnomad AFR AF: 0.0863

Gnomad AMI AF: 0.0932

Gnomad AMR AF: 0.0569

Gnomad ASJ AF: 0.0694

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0560

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0903

Gnomad OTH AF: 0.0673

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0831 AC: 12648 AN: 152186 Hom.: 579 Cov.: 32 AF XY: 0.0825 AC XY: 6137 AN XY: 74376

African (AFR) AF: 0.0861 AC: 3577 AN: 41530

American (AMR) AF: 0.0568 AC: 868 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0694 AC: 241 AN: 3472

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5180

South Asian (SAS) AF: 0.0559 AC: 269 AN: 4816

European-Finnish (FIN) AF: 0.123 AC: 1296 AN: 10562

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0903 AC: 6142 AN: 68020

Other (OTH) AF: 0.0666 AC: 141 AN: 2116

Alfa AF: 0.0871 Hom.: 79

Bravo AF: 0.0791

Asia WGS AF: 0.0250 AC: 87 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	19
DANN	Benign	0.91
PhyloP100		4.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs28727473; hg19: chr4-41751323;