1-2581777-C-T

Variant names:

• chr1-2581777-C-T
• rs734999
• ENST00000424215.1:n.91+127C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NR_121638.1(LOC100996583):​n.162+127C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.578 in 152,020 control chromosomes in the GnomAD database, including 26,883 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 0.58 (26881 hom., cov: 32)
  • Exomes 𝑓: 0.42 (2 hom.)
• Consequence: LOC100996583 NR_121638.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.202

Genes affected

ENSG00000228037 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.788 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC100996583	NR_121638.1	n.162+127C>T		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000228037	ENST00000424215.1	n.91+127C>T		intron_variant	Intron 1 of 2	5

Frequencies

GnomAD3 genomes AF: 0.577 AC: 87682 AN: 151842 Hom.: 26841 Cov.: 32

Gnomad AFR AF: 0.795

Gnomad AMI AF: 0.282

Gnomad AMR AF: 0.546

Gnomad ASJ AF: 0.452

Gnomad EAS AF: 0.540

Gnomad SAS AF: 0.659

Gnomad FIN AF: 0.500

Gnomad MID AF: 0.548

Gnomad NFE AF: 0.473

Gnomad OTH AF: 0.549

GnomAD4 exome AF: 0.417 AC: 25 AN: 60 Hom.: 2 AF XY: 0.344 AC XY: 11 AN XY: 32

Gnomad4 AFR exome AF: 0.500

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.389

Gnomad4 NFE exome AF: 0.421

GnomAD4 genome AF: 0.578 AC: 87774 AN: 151960 Hom.: 26881 Cov.: 32 AF XY: 0.579 AC XY: 42971 AN XY: 74220

Gnomad4 AFR AF: 0.795

Gnomad4 AMR AF: 0.546

Gnomad4 ASJ AF: 0.452

Gnomad4 EAS AF: 0.539

Gnomad4 SAS AF: 0.659

Gnomad4 FIN AF: 0.500

Gnomad4 NFE AF: 0.473

Gnomad4 OTH AF: 0.554

Alfa AF: 0.488 Hom.: 39979

Bravo AF: 0.584

Asia WGS AF: 0.680 AC: 2366 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.4
DANN	Benign	0.78

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs734999; hg19: chr1-2513216;