dbSNP rs17167492: LRGUK:c.588+106G>A (chr7-134143268-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_144648.3(LRGUK):c.588+106G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 706,352 control chromosomes in the GnomAD database, including 7,038 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 0.12 ( 1423 hom., cov: 33)

Exomes 𝑓: 0.13 ( 5615 hom. )

Consequence

LRGUK
NM_144648.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.43

Publications

3 publications found

Variant links:

Genes affected

LRGUK (HGNC:21964): (leucine rich repeats and guanylate kinase domain containing) Predicted to enable guanylate kinase activity. Predicted to be involved in axoneme assembly and spermatogenesis. Predicted to be located in acrosomal vesicle and manchette. Predicted to be active in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

LRGUK 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=-0.89).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.308 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144648.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
LRGUK	NM_144648.3	MANE Select	c.588+106G>A	intron	N/A	NP_653249.1	Q96M69
LRGUK	NM_001365700.3		c.588+106G>A	intron	N/A	NP_001352629.1	A0A8Q3SI13
LRGUK	NM_001365701.3		c.588+106G>A	intron	N/A	NP_001352630.1	A0A2R8YEJ5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
LRGUK	ENST00000285928.3	TSL:1 MANE Select	c.588+106G>A	intron	N/A	ENSP00000285928.2	Q96M69
LRGUK	ENST00000695542.2		c.588+106G>A	intron	N/A	ENSP00000511999.1	A0A8Q3SI13
LRGUK	ENST00000645682.1		c.588+106G>A	intron	N/A	ENSP00000495637.1	A0A2R8YEJ5

Frequencies

GnomAD3 genomes

AF:

0.122

AC:

18476

AN:

152030

Hom.:

1420

Cov.:

show subpopulations

Gnomad AFR

AF:

0.138

Gnomad AMI

AF:

0.0650

Gnomad AMR

AF:

0.159

Gnomad ASJ

AF:

0.142

Gnomad EAS

AF:

0.321

Gnomad SAS

AF:

0.174

Gnomad FIN

AF:

0.0598

Gnomad MID

AF:

0.127

Gnomad NFE

AF:

0.0929

Gnomad OTH

AF:

0.139

GnomAD4 exome

AF:

0.126

AC:

69654

AN:

554204

Hom.:

5615

AF XY:

0.127

AC XY:

38028

AN XY:

300108

show subpopulations

African (AFR)

AF:

0.140

AC:

2056

AN:

14736

American (AMR)

AF:

0.195

AC:

5439

AN:

27928

Ashkenazi Jewish (ASJ)

AF:

0.142

AC:

2346

AN:

16504

East Asian (EAS)

AF:

0.334

AC:

11567

AN:

34626

South Asian (SAS)

AF:

0.176

AC:

9507

AN:

53992

European-Finnish (FIN)

AF:

0.0684

AC:

3027

AN:

44270

Middle Eastern (MID)

AF:

0.141

AC:

423

AN:

3006

European-Non Finnish (NFE)

AF:

0.0954

AC:

31406

AN:

329376

Other (OTH)

AF:

0.130

AC:

3883

AN:

29766

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

2704

5409

8113

10818

13522

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

444

888

1332

1776

2220

<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:

0.122

AC:

18502

AN:

152148

Hom.:

1423

Cov.:

AF XY:

0.123

AC XY:

9121

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.138

AC:

5742

AN:

41522

American (AMR)

AF:

0.159

AC:

2432

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.142

AC:

494

AN:

3470

East Asian (EAS)

AF:

0.320

AC:

1655

AN:

5164

South Asian (SAS)

AF:

0.174

AC:

838

AN:

4812

European-Finnish (FIN)

AF:

0.0598

AC:

633

AN:

10586

Middle Eastern (MID)

AF:

0.136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0929

AC:

6320

AN:

68006

Other (OTH)

AF:

0.137

AC:

289

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

815

1631

2446

3262

4077

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

208

416

624

832

1040

<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:

0.111

Hom.:

153

Bravo

AF:

0.132

Asia WGS

AF:

0.229

AC:

794

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.14

(source)

DANN

Benign

0.55

PhyloP100

-1.4

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over