rs4666451

Variant names:

• chr2-19087182-G-A
• rs4666451
• ENST00000418165.5:n.352-2157C>T

Variant summary

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

The ENST00000418165.5(LINC01376):​n.352-2157C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.318 in 151,982 control chromosomes in the GnomAD database, including 8,408 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 0.32 (8408 hom., cov: 32)
• Consequence: LINC01376 ENST00000418165.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.651
• Publications: 22 publications found

Genes affected

LINC01376 (HGNC:50637): (long intergenic non-protein coding RNA 1376)

ENSG00000287284 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.394 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105373456	XR_007086234.1	n.1139-2055G>A		intron_variant	Intron 5 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LINC01376	ENST00000418165.5	n.352-2157C>T		intron_variant	Intron 2 of 4	4
LINC01376	ENST00000432142.6	n.638-2157C>T		intron_variant	Intron 2 of 5	4
LINC01376	ENST00000449124.1	n.242-21048C>T		intron_variant	Intron 2 of 4	2

Frequencies

GnomAD3 genomes AF: 0.319 AC: 48372 AN: 151864 Hom.: 8413 Cov.: 32

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.376

Gnomad ASJ AF: 0.331

Gnomad EAS AF: 0.0210

Gnomad SAS AF: 0.190

Gnomad FIN AF: 0.317

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.398

Gnomad OTH AF: 0.353

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

GnomAD4 genome AF: 0.318 AC: 48365 AN: 151982 Hom.: 8408 Cov.: 32 AF XY: 0.313 AC XY: 23253 AN XY: 74300

African (AFR) AF: 0.216 AC: 8939 AN: 41432

American (AMR) AF: 0.376 AC: 5734 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.331 AC: 1149 AN: 3470

East Asian (EAS) AF: 0.0211 AC: 109 AN: 5178

South Asian (SAS) AF: 0.192 AC: 924 AN: 4816

European-Finnish (FIN) AF: 0.317 AC: 3345 AN: 10546

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.398 AC: 27053 AN: 67954

Other (OTH) AF: 0.350 AC: 740 AN: 2116

Alfa AF: 0.378 Hom.: 18425

Bravo AF: 0.318

Asia WGS AF: 0.135 AC: 471 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.30
DANN	Benign	0.22
PhyloP100		-0.65

Splicing

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

Other links and lift over

dbSNP: rs4666451; hg19: chr2-19286943;