13-43933553-T-C

Variant summary

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

The ENST00000439707.6(NRAD1):n.99+14120T>C variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 152,030 control chromosomes in the GnomAD database, including 7,254 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 0.30 (7254 hom., cov: 32)
• Consequence: NRAD1 ENST00000439707.6 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.980

Genes affected

NRAD1 (HGNC:26981): (non-coding RNA in the aldehyde dehydrogenase 1A pathway)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.5 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NRAD1	ENST00000439707.6	n.99+14120T>C		intron_variant, non_coding_transcript_variant		5
NRAD1	ENST00000585327.5	n.64-8870T>C		intron_variant, non_coding_transcript_variant		5
NRAD1	ENST00000620454.4	n.158-8870T>C		intron_variant, non_coding_transcript_variant		4
NRAD1	ENST00000629019.2	n.108+11874T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.296 AC: 44951 AN: 151912 Hom.: 7224 Cov.: 32

Gnomad AFR AF: 0.391

Gnomad AMI AF: 0.428

Gnomad AMR AF: 0.330

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.517

Gnomad SAS AF: 0.321

Gnomad FIN AF: 0.232

Gnomad MID AF: 0.369

Gnomad NFE AF: 0.222

Gnomad OTH AF: 0.316

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

GnomAD4 genome AF: 0.296 AC: 45028 AN: 152030 Hom.: 7254 Cov.: 32 AF XY: 0.301 AC XY: 22394 AN XY: 74322

Gnomad4 AFR AF: 0.391

Gnomad4 AMR AF: 0.330

Gnomad4 ASJ AF: 0.236

Gnomad4 EAS AF: 0.516

Gnomad4 SAS AF: 0.321

Gnomad4 FIN AF: 0.232

Gnomad4 NFE AF: 0.222

Gnomad4 OTH AF: 0.321

Alfa AF: 0.241 Hom.: 9541

Bravo AF: 0.307

Asia WGS AF: 0.469 AC: 1631 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	12
Dann	Benign	0.88

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

Publications

LitVar

Other links and lift over

dbSNP: rs687582; hg19: chr13-44507689;