ENST00000435493.3:n.254+2121T>A

Variant names:

• chr21-41166422-A-T
• rs9975138
• ENST00000435493.3:n.254+2121T>A

Variant summary

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

The ENST00000435493.3(LINC00323):​n.254+2121T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 152,074 control chromosomes in the GnomAD database, including 2,165 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 0.16 (2165 hom., cov: 32)
• Consequence: LINC00323 ENST00000435493.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.338
• Publications: 2 publications found

Genes affected

LINC00323 (HGNC:19720): (long intergenic non-protein coding RNA 323)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.225 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LINC00323	ENST00000435493.3	n.254+2121T>A		intron_variant	Intron 1 of 3	3
LINC00323	ENST00000836835.1	n.246+2121T>A		intron_variant	Intron 1 of 3
LINC00323	ENST00000836836.1	n.167+2121T>A		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24774 AN: 151956 Hom.: 2165 Cov.: 32

Gnomad AFR AF: 0.229

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.236

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.189

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

GnomAD4 genome AF: 0.163 AC: 24777 AN: 152074 Hom.: 2165 Cov.: 32 AF XY: 0.161 AC XY: 11999 AN XY: 74326

African (AFR) AF: 0.229 AC: 9497 AN: 41492

American (AMR) AF: 0.121 AC: 1853 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.163 AC: 564 AN: 3470

East Asian (EAS) AF: 0.236 AC: 1217 AN: 5162

South Asian (SAS) AF: 0.150 AC: 720 AN: 4806

European-Finnish (FIN) AF: 0.112 AC: 1185 AN: 10586

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.135 AC: 9168 AN: 67976

Other (OTH) AF: 0.186 AC: 392 AN: 2104

Alfa AF: 0.145 Hom.: 249

Bravo AF: 0.168

Asia WGS AF: 0.154 AC: 540 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.58
DANN	Benign	0.29
PhyloP100		-0.34

Splicing

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

Other links and lift over

dbSNP: rs9975138; hg19: chr21-42538349;