rs28727473

Positions:

• chr4-41749306-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The ENST00000508038.1(PHOX2B-AS1):​n.294+720G>A variant causes a intron, non coding transcript 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 ENST00000508038.1 intron, non_coding_transcript
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.08

Genes affected

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

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PHOX2B-AS1	XR_001741671.2	n.238+720G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PHOX2B-AS1	ENST00000508038.1	n.294+720G>A		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.0861

Gnomad4 AMR AF: 0.0568

Gnomad4 ASJ AF: 0.0694

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.0559

Gnomad4 FIN AF: 0.123

Gnomad4 NFE AF: 0.0903

Gnomad4 OTH AF: 0.0666

Alfa AF: 0.0871 Hom.: 79

Bravo AF: 0.0791

Asia WGS AF: 0.0250 AC: 87 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 02, 2019

- -

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs28727473; hg19: chr4-41751323;