rs219391

Positions:

• chr14-60018213-C-T

Variant summary

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

The ENST00000570145.2(LRRC9):​c.3318-158C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.792 in 556,160 control chromosomes in the GnomAD database, including 179,202 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 0.75 (44458 hom., cov: 32)
  • Exomes 𝑓: 0.81 (134744 hom.)
• Consequence: LRRC9 ENST00000570145.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0150

Genes affected

LRRC9 (HGNC:19848): (leucine rich repeat containing 9)

PCNX4-DT (HGNC:55447): (PCNX4 divergent transcript)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.862 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRC9	NM_001395648.1	c.3318-158C>T		intron_variant		ENST00000570145.2	NP_001382577.1
LRRC9	NR_075071.3	n.3522-133C>T		intron_variant, non_coding_transcript_variant
PCNX4-DT	XR_943918.4	n.261+12083G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRC9	ENST00000570145.2	c.3318-158C>T		intron_variant		3	NM_001395648.1	ENSP00000457773	P1
PCNX4-DT	ENST00000554123.1	n.164+12083G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.747 AC: 113378 AN: 151722 Hom.: 44450 Cov.: 32

Gnomad AFR AF: 0.496

Gnomad AMI AF: 0.908

Gnomad AMR AF: 0.828

Gnomad ASJ AF: 0.808

Gnomad EAS AF: 0.656

Gnomad SAS AF: 0.635

Gnomad FIN AF: 0.899

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.868

Gnomad OTH AF: 0.754

GnomAD4 exome AF: 0.809 AC: 327073 AN: 404320 Hom.: 134744 AF XY: 0.802 AC XY: 172362 AN XY: 214924

Gnomad4 AFR exome AF: 0.496

Gnomad4 AMR exome AF: 0.858

Gnomad4 ASJ exome AF: 0.807

Gnomad4 EAS exome AF: 0.617

Gnomad4 SAS exome AF: 0.643

Gnomad4 FIN exome AF: 0.893

Gnomad4 NFE exome AF: 0.863

Gnomad4 OTH exome AF: 0.794

GnomAD4 genome AF: 0.747 AC: 113413 AN: 151840 Hom.: 44458 Cov.: 32 AF XY: 0.746 AC XY: 55377 AN XY: 74194

Gnomad4 AFR AF: 0.495

Gnomad4 AMR AF: 0.828

Gnomad4 ASJ AF: 0.808

Gnomad4 EAS AF: 0.655

Gnomad4 SAS AF: 0.637

Gnomad4 FIN AF: 0.899

Gnomad4 NFE AF: 0.868

Gnomad4 OTH AF: 0.755

Alfa AF: 0.805 Hom.: 6301

Bravo AF: 0.736

Asia WGS AF: 0.629 AC: 2179 AN: 3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.1
DANN	Benign	0.58

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: rs219391; hg19: chr14-60484931;