rs2738751

Positions:

• chr1-220878371-C-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000691443.1(ENSG00000289142):​n.831G>C 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 0.154 in 152,092 control chromosomes in the GnomAD database, including 1,976 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 0.15 (1976 hom., cov: 32)
• Consequence: ENST00000691443.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.29

Genes affected

(HGNC:):

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

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.2 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLX-AS1	NR_046901.1	n.292+1478G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000691443.1	n.831G>C		non_coding_transcript_exon_variant	1/1
HLX-AS1	ENST00000552026.1	n.292+1478G>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23441 AN: 151974 Hom.: 1968 Cov.: 32

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.0779

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.221

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0525

Gnomad FIN AF: 0.110

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.168

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

GnomAD4 genome AF: 0.154 AC: 23472 AN: 152092 Hom.: 1976 Cov.: 32 AF XY: 0.150 AC XY: 11141 AN XY: 74358

Gnomad4 AFR AF: 0.204

Gnomad4 AMR AF: 0.137

Gnomad4 ASJ AF: 0.221

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0525

Gnomad4 FIN AF: 0.110

Gnomad4 NFE AF: 0.151

Gnomad4 OTH AF: 0.165

Alfa AF: 0.153 Hom.: 234

Bravo AF: 0.162

Asia WGS AF: 0.0420 AC: 147 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	14
DANN	Benign	0.79

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2738751; hg19: chr1-221051713;