Genetic Variant NM_014665.4:c.*766T>C (chr8-144522244-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014665.4(LRRC14):c.*766T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.485 in 522,390 control chromosomes in the GnomAD database, including 62,074 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 0.49 ( 18365 hom., cov: 34)

Exomes 𝑓: 0.48 ( 43709 hom. )

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: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.04).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.55 is higher than 0.05.

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>C	3_prime_UTR	Exon 4 of 4	NP_055480.1
LRRC14	NM_001272036.2		c.*766T>C	3_prime_UTR	Exon 5 of 5	NP_001258965.1
LRRC24	NM_001024678.4	MANE Select	c.*231A>G	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>C	3_prime_UTR	Exon 4 of 4	ENSP00000292524.1
LRRC14	ENST00000887351.1		c.*766T>C	3_prime_UTR	Exon 5 of 5	ENSP00000557410.1
LRRC14	ENST00000927377.1		c.*766T>C	3_prime_UTR	Exon 3 of 3	ENSP00000597436.1

Frequencies

GnomAD3 genomes

AF:

0.489

AC:

73658

AN:

150622

Hom.:

18349

Cov.:

show subpopulations

Gnomad AFR

AF:

0.556

Gnomad AMI

AF:

0.643

Gnomad AMR

AF:

0.420

Gnomad ASJ

AF:

0.600

Gnomad EAS

AF:

0.342

Gnomad SAS

AF:

0.376

Gnomad FIN

AF:

0.465

Gnomad MID

AF:

0.671

Gnomad NFE

AF:

0.477

Gnomad OTH

AF:

0.509

GnomAD4 exome

AF:

0.483

AC:

179668

AN:

371650

Hom.:

43709

Cov.:

AF XY:

0.483

AC XY:

90909

AN XY:

188194

show subpopulations

African (AFR)

AF:

0.562

AC:

5055

AN:

9002

American (AMR)

AF:

0.388

AC:

2802

AN:

7222

Ashkenazi Jewish (ASJ)

AF:

0.604

AC:

6243

AN:

10332

East Asian (EAS)

AF:

0.285

AC:

6385

AN:

22404

South Asian (SAS)

AF:

0.428

AC:

6132

AN:

14336

European-Finnish (FIN)

AF:

0.459

AC:

10733

AN:

23386

Middle Eastern (MID)

AF:

0.681

AC:

1090

AN:

1600

European-Non Finnish (NFE)

AF:

0.498

AC:

130819

AN:

262728

Other (OTH)

AF:

0.504

AC:

10409

AN:

20640

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

4535

9071

13606

18142

22677

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2138

4276

6414

8552

10690

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.489

AC:

73709

AN:

150740

Hom.:

18365

Cov.:

AF XY:

0.485

AC XY:

35668

AN XY:

73576

show subpopulations

African (AFR)

AF:

0.556

AC:

22892

AN:

41180

American (AMR)

AF:

0.420

AC:

6340

AN:

15108

Ashkenazi Jewish (ASJ)

AF:

0.600

AC:

2076

AN:

3462

East Asian (EAS)

AF:

0.342

AC:

1735

AN:

5074

South Asian (SAS)

AF:

0.377

AC:

1791

AN:

4752

European-Finnish (FIN)

AF:

0.465

AC:

4852

AN:

10428

Middle Eastern (MID)

AF:

0.670

AC:

197

AN:

294

European-Non Finnish (NFE)

AF:

0.477

AC:

32169

AN:

67426

Other (OTH)

AF:

0.509

AC:

1072

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1993

3986

5980

7973

9966

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

654

1308

1962

2616

3270

<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:

0.479

Hom.:

21828

Bravo

AF:

0.487

Asia WGS

AF:

0.374

AC:

1304

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

2.2

(source)

DANN

Benign

0.61

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over