Genetic Variant LRRC14:c.*766T>A (chr8-144522244-T-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_014665.4(LRRC14):c.*766T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000133 in 150,670 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000013 ( 0 hom., cov: 34)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

LRRC14
NM_014665.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.17

Publications

12 publications found

Variant links:

Genes affected

LRRC14 (HGNC:20419): (leucine rich repeat containing 14) This gene encodes a leucine-rich repeat-containing protein. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Dec 2012]

LRRC14 links:

LRRC24 (HGNC:28947): (leucine rich repeat containing 24) Predicted to act upstream of or within positive regulation of synapse assembly. Predicted to be integral component of membrane. Predicted to be active in extracellular matrix and extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

LRRC24 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.01).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014665.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
LRRC14	NM_014665.4	MANE Select	c.*766T>A	3_prime_UTR	Exon 4 of 4	NP_055480.1
LRRC14	NM_001272036.2		c.*766T>A	3_prime_UTR	Exon 5 of 5	NP_001258965.1
LRRC24	NM_001024678.4	MANE Select	c.*231A>T	downstream_gene	N/A	NP_001019849.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
LRRC14	ENST00000292524.6	TSL:1 MANE Select	c.*766T>A	3_prime_UTR	Exon 4 of 4	ENSP00000292524.1
LRRC14	ENST00000887351.1		c.*766T>A	3_prime_UTR	Exon 5 of 5	ENSP00000557410.1
LRRC14	ENST00000927377.1		c.*766T>A	3_prime_UTR	Exon 3 of 3	ENSP00000597436.1

Frequencies

GnomAD3 genomes

AF:

0.0000133

AC:

AN:

150670

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000487

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

372520

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

188638

African (AFR)

AF:

0.00

AC:

AN:

9018

American (AMR)

AF:

0.00

AC:

AN:

7240

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

10362

East Asian (EAS)

AF:

0.00

AC:

AN:

22444

South Asian (SAS)

AF:

0.00

AC:

AN:

14362

European-Finnish (FIN)

AF:

0.00

AC:

AN:

23430

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1606

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

263378

Other (OTH)

AF:

0.00

AC:

AN:

20680

GnomAD4 genome

AF:

0.0000133

AC:

AN:

150670

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73474

show subpopulations

African (AFR)

AF:

0.0000487

AC:

AN:

41070

American (AMR)

AF:

0.00

AC:

AN:

15092

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3462

East Asian (EAS)

AF:

0.00

AC:

AN:

5088

South Asian (SAS)

AF:

0.00

AC:

AN:

4762

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10442

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67444

Other (OTH)

AF:

0.00

AC:

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

21828

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

1.8

(source)

DANN

Benign

0.64

PhyloP100

-3.2

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over