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GeneBe

14-60057997-C-T

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

2

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

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.45).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=1.22 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
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
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 4 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
LRRC9NM_001395648.1 linkuse as main transcriptc.4251C>T p.Asp1417= synonymous_variant 31/33 ENST00000570145.2
LRRC9NR_075071.3 linkuse as main transcriptn.4484C>T non_coding_transcript_exon_variant 31/33
PCNX4-DTXR_943918.4 linkuse as main transcriptn.45-347G>A intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
LRRC9ENST00000570145.2 linkuse as main transcriptc.4251C>T p.Asp1417= synonymous_variant 31/333 NM_001395648.1 P1
PCNX4-DTENST00000554123.1 linkuse as main transcriptn.82-27619G>A intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00568
AC:
863
AN:
152060
Hom.:
4
Cov.:
32
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.:
6
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.:
25
Cov.:
0
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
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00566
AC:
862
AN:
152178
Hom.:
4
Cov.:
32
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.:
4
Bravo
AF:
0.00553
Asia WGS
AF:
0.00202
AC:
7
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 submitterclinical testingCeGaT Center for Human Genetics TuebingenJan 01, 2023LRRC9: 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.

Other links and lift over

dbSNP: rs45545035; hg19: chr14-60524715; COSMIC: COSV99579193; COSMIC: COSV99579193; API