rs28462174

Variant names:

• chr4-41749194-G-A
• rs28462174
• ENST00000819359.1:n.65G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000819356.1(PHOX2B-AS1):​n.239-6G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0937 in 151,838 control chromosomes in the GnomAD database, including 729 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.094 (729 hom., cov: 32)
• Consequence: PHOX2B-AS1 ENST00000819356.1 splice_region, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.275
• Publications: 1 publications found

Genes affected

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

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 4-41749194-G-A is Benign according to our data. Variant chr4-41749194-G-A is described in ClinVar as Benign. ClinVar VariationId is 1265356.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.119 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHOX2B-AS1	NR_187403.1		n.238+608G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHOX2B-AS1	ENST00000819359.1		n.65G>A		non_coding_transcript_exon	Exon 1 of 5
	PHOX2B-AS1	ENST00000508038.2	TSL:5	n.294+608G>A		intron	N/A
	PHOX2B-AS1	ENST00000819353.1		n.241+608G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0938 AC: 14230 AN: 151718 Hom.: 731 Cov.: 32

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.0932

Gnomad AMR AF: 0.0633

Gnomad ASJ AF: 0.0695

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0560

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.0801

Gnomad NFE AF: 0.0905

Gnomad OTH AF: 0.0739

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

GnomAD4 genome AF: 0.0937 AC: 14233 AN: 151838 Hom.: 729 Cov.: 32 AF XY: 0.0926 AC XY: 6868 AN XY: 74206

African (AFR) AF: 0.122 AC: 5046 AN: 41332

American (AMR) AF: 0.0632 AC: 966 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0695 AC: 241 AN: 3470

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5182

South Asian (SAS) AF: 0.0558 AC: 268 AN: 4802

European-Finnish (FIN) AF: 0.123 AC: 1291 AN: 10512

Middle Eastern (MID) AF: 0.0822 AC: 24 AN: 292

European-Non Finnish (NFE) AF: 0.0906 AC: 6154 AN: 67950

Other (OTH) AF: 0.0731 AC: 154 AN: 2106

Alfa AF: 0.0940 Hom.: 93

Bravo AF: 0.0917

ClinVar

ClinVar submissions

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	-0.95
CADD	Benign	7.1
DANN	Benign	0.78
PhyloP100		0.28
PromoterAI		-0.0082	Neutral

Splicing

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

Other links and lift over

dbSNP: rs28462174; hg19: chr4-41751211;