rs2494493

Variant names:

• chr1-159840450-A-C
• rs2494493
• ENST00000645519.1:n.*1655T>G

Variant summary

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

The ENST00000645519.1(ENSG00000256029):​n.*1655T>G 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 0.139 in 1,207,964 control chromosomes in the GnomAD database, including 21,386 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 0.26 (8116 hom., cov: 32)
  • Exomes 𝑓: 0.12 (13270 hom.)
• Consequence: ENSG00000256029 ENST00000645519.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0970
• Publications: 4 publications found

Genes affected

ENSG00000256029 (HGNC:):

SNHG28 (HGNC:27647): (small nucleolar RNA host gene 28) Enables RNA binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.548 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000645519.1. 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
	SNHG28	NR_147122.1		n.391+676T>G		intron	N/A
	SNHG28	NR_147123.1		n.226+676T>G		intron	N/A
	SNHG28	NR_147124.1		n.282-2423T>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000256029	ENST00000645519.1		n.*1655T>G		non_coding_transcript_exon	Exon 9 of 9	ENSP00000494894.1
	SNHG28	ENST00000674949.1		n.603T>G		non_coding_transcript_exon	Exon 3 of 4
	SNHG28	ENST00000675503.1		n.586T>G		non_coding_transcript_exon	Exon 3 of 4

Frequencies

GnomAD3 genomes AF: 0.257 AC: 39028 AN: 151584 Hom.: 8106 Cov.: 32

Gnomad AFR AF: 0.555

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.530

Gnomad SAS AF: 0.262

Gnomad FIN AF: 0.125

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.0995

Gnomad OTH AF: 0.235

GnomAD4 exome AF: 0.122 AC: 128450 AN: 1056262 Hom.: 13270 Cov.: 31 AF XY: 0.122 AC XY: 60721 AN XY: 499636

African (AFR) AF: 0.582 AC: 13070 AN: 22466

American (AMR) AF: 0.181 AC: 1728 AN: 9572

Ashkenazi Jewish (ASJ) AF: 0.162 AC: 2073 AN: 12814

East Asian (EAS) AF: 0.557 AC: 10752 AN: 19314

South Asian (SAS) AF: 0.234 AC: 7418 AN: 31660

European-Finnish (FIN) AF: 0.107 AC: 1514 AN: 14140

Middle Eastern (MID) AF: 0.198 AC: 533 AN: 2690

European-Non Finnish (NFE) AF: 0.0935 AC: 84362 AN: 902170

Other (OTH) AF: 0.169 AC: 7000 AN: 41436

GnomAD4 genome AF: 0.258 AC: 39069 AN: 151702 Hom.: 8116 Cov.: 32 AF XY: 0.258 AC XY: 19157 AN XY: 74130

African (AFR) AF: 0.554 AC: 22892 AN: 41292

American (AMR) AF: 0.191 AC: 2914 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.160 AC: 555 AN: 3468

East Asian (EAS) AF: 0.530 AC: 2712 AN: 5120

South Asian (SAS) AF: 0.261 AC: 1256 AN: 4806

European-Finnish (FIN) AF: 0.125 AC: 1314 AN: 10552

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.0995 AC: 6756 AN: 67890

Other (OTH) AF: 0.233 AC: 492 AN: 2110

Alfa AF: 0.147 Hom.: 1495

Bravo AF: 0.275

Asia WGS AF: 0.415 AC: 1441 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.9
DANN	Benign	0.54
PhyloP100		-0.097
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs2494493; hg19: chr1-159810240;