Variant 14-60057997-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The ENST00000570145.2(LRRC9):c.4251C>T(p.Asp1417=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00702 in 653,748 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0057 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0074 ( 25 hom. )

Consequence

LRRC9
ENST00000570145.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.22

Variant links:

Genes affected

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

LRRC9 links:

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

PCNX4-DT links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP6

Variant 14-60057997-C-T is Benign according to our data. Variant chr14-60057997-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2644264.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=1.22 with no splicing effect.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00744 (3730/501570) while in subpopulation MID AF= 0.0268 (104/3880). AF 95% confidence interval is 0.0226. There are 25 homozygotes in gnomad4_exome. There are 2003 alleles in male gnomad4_exome subpopulation. Median coverage is 0. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
LRRC9	NM_001395648.1 linkuse as main transcript	c.4251C>T	p.Asp1417=	synonymous_variant	31/33	ENST00000570145.2	NP_001382577.1
LRRC9	NR_075071.3 linkuse as main transcript	n.4484C>T		non_coding_transcript_exon_variant	31/33
PCNX4-DT	XR_943918.4 linkuse as main transcript	n.45-347G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRC9	ENST00000570145.2 linkuse as main transcript	c.4251C>T	p.Asp1417=	synonymous_variant	31/33	3	NM_001395648.1	ENSP00000457773	P1
PCNX4-DT	ENST00000554123.1 linkuse as main transcript	n.82-27619G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00568

AC:

863

AN:

152060

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00544

Gnomad ASJ

AF:

0.0222

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.00113

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.00887

Gnomad OTH

AF:

0.00526

GnomAD3 exomes

AF:

0.00671

AC:

892

AN:

132952

Hom.:

AF XY:

0.00676

AC XY:

490

AN XY:

72472

show subpopulations

Gnomad AFR exome

AF:

0.00156

Gnomad AMR exome

AF:

0.00323

Gnomad ASJ exome

AF:

0.0231

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00206

Gnomad FIN exome

AF:

0.00150

Gnomad NFE exome

AF:

0.00995

Gnomad OTH exome

AF:

0.0105

GnomAD4 exome

AF:

0.00744

AC:

3730

AN:

501570

Hom.:

Cov.:

AF XY:

0.00740

AC XY:

2003

AN XY:

270536

show subpopulations

Gnomad4 AFR exome

AF:

0.00208

Gnomad4 AMR exome

AF:

0.00350

Gnomad4 ASJ exome

AF:

0.0223

Gnomad4 EAS exome

AF:

0.0000633

Gnomad4 SAS exome

AF:

0.00173

Gnomad4 FIN exome

AF:

0.00146

Gnomad4 NFE exome

AF:

0.00943

Gnomad4 OTH exome

AF:

0.00868

GnomAD4 genome

AF:

0.00566

AC:

862

AN:

152178

Hom.:

Cov.:

AF XY:

0.00562

AC XY:

418

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.00144

Gnomad4 AMR

AF:

0.00543

Gnomad4 ASJ

AF:

0.0222

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00208

Gnomad4 FIN

AF:

0.00113

Gnomad4 NFE

AF:

0.00887

Gnomad4 OTH

AF:

0.00520

Alfa

AF:

0.00979

Hom.:

Bravo

AF:

0.00553

Asia WGS

AF:

0.00202

AC:

AN:

3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

LRRC9: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

5.4

DANN

Benign

0.48

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over