dbSNP rs9071: LRRC14:c.*3644G>A (chr8-144525122-G-A) – 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.*3644G>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 0.486 in 793,018 control chromosomes in the GnomAD database, including 96,068 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 0.54 ( 22648 hom., cov: 35)

Exomes 𝑓: 0.47 ( 73420 hom. )

Consequence

LRRC14
NM_014665.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.275

Publications

25 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:

Genome browser will be placed here

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=-0.82).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.643 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC14	NM_014665.4 link	c.*3644G>A		3_prime_UTR_variant	Exon 4 of 4	ENST00000292524.6	NP_055480.1	Q15048
LRRC24	NM_001024678.4 link	c.-59-89C>T		intron_variant	Intron 1 of 4	ENST00000529415.7	NP_001019849.2	Q50LG9

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
LRRC14	ENST00000292524.6 link	c.*3644G>A	3_prime_UTR_variant	Exon 4 of 4	1	NM_014665.4	ENSP00000292524.1	Q15048
LRRC24	ENST00000529415.7 link	c.-59-89C>T	intron_variant	Intron 1 of 4	1	NM_001024678.4	ENSP00000434849.1	Q50LG9
LRRC24	ENST00000533758.1 link	c.-59-89C>T	intron_variant	Intron 1 of 4	5		ENSP00000435653.1	G3V1D8

Frequencies

GnomAD3 genomes

AF:

0.539

AC:

81940

AN:

152100

Hom.:

22614

Cov.:

show subpopulations

Gnomad AFR

AF:

0.649

Gnomad AMI

AF:

0.269

Gnomad AMR

AF:

0.566

Gnomad ASJ

AF:

0.480

Gnomad EAS

AF:

0.481

Gnomad SAS

AF:

0.587

Gnomad FIN

AF:

0.501

Gnomad MID

AF:

0.465

Gnomad NFE

AF:

0.479

Gnomad OTH

AF:

0.535

GnomAD4 exome

AF:

0.473

AC:

303029

AN:

640800

Hom.:

73420

Cov.:

AF XY:

0.476

AC XY:

150469

AN XY:

316250

show subpopulations

African (AFR)

AF:

0.637

AC:

8495

AN:

13330

American (AMR)

AF:

0.561

AC:

5756

AN:

10266

Ashkenazi Jewish (ASJ)

AF:

0.478

AC:

5999

AN:

12556

East Asian (EAS)

AF:

0.410

AC:

10416

AN:

25374

South Asian (SAS)

AF:

0.572

AC:

14159

AN:

24736

European-Finnish (FIN)

AF:

0.495

AC:

12696

AN:

25654

Middle Eastern (MID)

AF:

0.419

AC:

922

AN:

2200

European-Non Finnish (NFE)

AF:

0.463

AC:

229857

AN:

496452

Other (OTH)

AF:

0.487

AC:

14729

AN:

30232

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

8053

16107

24160

32214

40267

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5906

11812

17718

23624

29530

<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:

0.539

AC:

82024

AN:

152218

Hom.:

22648

Cov.:

AF XY:

0.543

AC XY:

40382

AN XY:

74426

show subpopulations

African (AFR)

AF:

0.649

AC:

26966

AN:

41540

American (AMR)

AF:

0.567

AC:

8669

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.480

AC:

1664

AN:

3470

East Asian (EAS)

AF:

0.480

AC:

2486

AN:

5180

South Asian (SAS)

AF:

0.588

AC:

2839

AN:

4830

European-Finnish (FIN)

AF:

0.501

AC:

5308

AN:

10600

Middle Eastern (MID)

AF:

0.469

AC:

138

AN:

294

European-Non Finnish (NFE)

AF:

0.479

AC:

32583

AN:

67992

Other (OTH)

AF:

0.534

AC:

1126

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

2000

4001

6001

8002

10002

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

704

1408

2112

2816

3520

<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:

0.501

Hom.:

59487

Bravo

AF:

0.547

Asia WGS

AF:

0.578

AC:

2009

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

3.3

(source)

DANN

Benign

0.67

PhyloP100

0.28

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over