14-59988697-C-T

Variant names:

• chr14-59988697-C-T
• rs219349
• NM_001395648.1:c.2211+3473C>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.2211+3473C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.742 in 151,986 control chromosomes in the GnomAD database, including 44,133 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 0.74 (44133 hom., cov: 32)
• Consequence: LRRC9 NM_001395648.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.152
• Publications: 3 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.862 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.2211+3473C>T		intron	N/A	NP_001382577.1
	LRRC9	NM_001355272.3		c.2211+3473C>T		intron	N/A	NP_001342201.1
	LRRC9	NR_075071.3		n.2415+3473C>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.2211+3473C>T		intron	N/A	ENSP00000457773.2
	LRRC9	ENST00000647410.1		c.2211+3473C>T		intron	N/A	ENSP00000493790.1
	LRRC9	ENST00000445360.5	TSL:5	c.2211+3473C>T		intron	N/A	ENSP00000454748.1

Frequencies

GnomAD3 genomes AF: 0.743 AC: 112771 AN: 151870 Hom.: 44125 Cov.: 32

Gnomad AFR AF: 0.480

Gnomad AMI AF: 0.908

Gnomad AMR AF: 0.826

Gnomad ASJ AF: 0.806

Gnomad EAS AF: 0.651

Gnomad SAS AF: 0.634

Gnomad FIN AF: 0.898

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.868

Gnomad OTH AF: 0.750

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

GnomAD4 genome AF: 0.742 AC: 112806 AN: 151986 Hom.: 44133 Cov.: 32 AF XY: 0.742 AC XY: 55123 AN XY: 74308

African (AFR) AF: 0.480 AC: 19871 AN: 41420

American (AMR) AF: 0.826 AC: 12620 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.806 AC: 2800 AN: 3472

East Asian (EAS) AF: 0.650 AC: 3358 AN: 5164

South Asian (SAS) AF: 0.635 AC: 3059 AN: 4814

European-Finnish (FIN) AF: 0.898 AC: 9494 AN: 10568

Middle Eastern (MID) AF: 0.726 AC: 212 AN: 292

European-Non Finnish (NFE) AF: 0.868 AC: 58980 AN: 67960

Other (OTH) AF: 0.751 AC: 1584 AN: 2110

Alfa AF: 0.791 Hom.: 6383

Bravo AF: 0.730

Asia WGS AF: 0.622 AC: 2146 AN: 3446

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.6
DANN	Benign	0.47
PhyloP100		-0.15
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: rs219349; hg19: chr14-60455415;