14-59976472-C-T

Variant names:

• chr14-59976472-C-T
• rs219326
• NM_001395648.1:c.1640-753C>T

Variant summary

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

The NM_001395648.1(LRRC9):​c.1640-753C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.761 in 152,054 control chromosomes in the GnomAD database, including 45,861 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 0.76 (45861 hom., cov: 31)
• Consequence: LRRC9 NM_001395648.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.296
• Publications: 10 publications found

Genes affected

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

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.863 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001395648.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC9	NM_001395648.1	MANE Select	c.1640-753C>T		intron	N/A	NP_001382577.1	H3BUS4
	LRRC9	NM_001355272.3		c.1640-753C>T		intron	N/A	NP_001342201.1	H3BUS4
	LRRC9	NR_075071.3		n.1844-753C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC9	ENST00000570145.2	TSL:3 MANE Select	c.1640-753C>T		intron	N/A	ENSP00000457773.2	H3BUS4
	LRRC9	ENST00000647410.1		c.1640-753C>T		intron	N/A	ENSP00000493790.1	H3BUS4
	LRRC9	ENST00000445360.5	TSL:5	c.1640-753C>T		intron	N/A	ENSP00000454748.1	Q6ZRR7-1

Frequencies

GnomAD3 genomes AF: 0.762 AC: 115705 AN: 151936 Hom.: 45857 Cov.: 31

Gnomad AFR AF: 0.522

Gnomad AMI AF: 0.908

Gnomad AMR AF: 0.832

Gnomad ASJ AF: 0.811

Gnomad EAS AF: 0.806

Gnomad SAS AF: 0.664

Gnomad FIN AF: 0.899

Gnomad MID AF: 0.734

Gnomad NFE AF: 0.868

Gnomad OTH AF: 0.763

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

GnomAD4 genome AF: 0.761 AC: 115736 AN: 152054 Hom.: 45861 Cov.: 31 AF XY: 0.761 AC XY: 56572 AN XY: 74318

African (AFR) AF: 0.522 AC: 21603 AN: 41410

American (AMR) AF: 0.832 AC: 12727 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.811 AC: 2815 AN: 3470

East Asian (EAS) AF: 0.805 AC: 4159 AN: 5166

South Asian (SAS) AF: 0.665 AC: 3203 AN: 4818

European-Finnish (FIN) AF: 0.899 AC: 9522 AN: 10588

Middle Eastern (MID) AF: 0.724 AC: 213 AN: 294

European-Non Finnish (NFE) AF: 0.868 AC: 59057 AN: 68004

Other (OTH) AF: 0.765 AC: 1611 AN: 2106

Alfa AF: 0.833 Hom.: 83714

Bravo AF: 0.751

Asia WGS AF: 0.710 AC: 2472 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.85
DANN	Benign	0.68
PhyloP100		-0.30
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs219326; hg19: chr14-60443190;