1-220878450-C-T

Variant names:

• chr1-220878450-C-T
• rs3806325
• ENST00000651706.1:n.843-2744C>T

Variant summary

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

The ENST00000651706.1(ENSG00000286231):​n.843-2744C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 152,194 control chromosomes in the GnomAD database, including 1,883 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 0.14 (1883 hom., cov: 32)
• Consequence: ENSG00000286231 ENST00000651706.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.198
• Publications: 9 publications found

Genes affected

ENSG00000286231 (HGNC:):

HLX-AS1 (HGNC:42509): (HLX antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLX-AS1	NR_046901.1	n.292+1399G>A		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000286231	ENST00000651706.1	n.843-2744C>T		intron_variant	Intron 6 of 8			ENSP00000499157.1

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20892 AN: 152076 Hom.: 1883 Cov.: 32

Gnomad AFR AF: 0.0388

Gnomad AMI AF: 0.282

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.205

Gnomad EAS AF: 0.0656

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.258

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.128

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

GnomAD4 genome AF: 0.137 AC: 20891 AN: 152194 Hom.: 1883 Cov.: 32 AF XY: 0.137 AC XY: 10202 AN XY: 74396

African (AFR) AF: 0.0387 AC: 1608 AN: 41554

American (AMR) AF: 0.114 AC: 1751 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.205 AC: 712 AN: 3468

East Asian (EAS) AF: 0.0657 AC: 340 AN: 5172

South Asian (SAS) AF: 0.132 AC: 638 AN: 4822

European-Finnish (FIN) AF: 0.258 AC: 2727 AN: 10574

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.185 AC: 12557 AN: 67986

Other (OTH) AF: 0.127 AC: 268 AN: 2110

Alfa AF: 0.161 Hom.: 3764

Bravo AF: 0.122

Asia WGS AF: 0.0950 AC: 331 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	7.7
DANN	Benign	0.87
PhyloP100		-0.20
Mutation Taster		=300/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs3806325; hg19: chr1-221051792;