dbSNP rs9841322: KALRN:p.Lys683Lys (chr3-124395221-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6BP7BA1

The NM_001388419.1(KALRN):c.2049G>A(p.Lys683Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 1,612,574 control chromosomes in the GnomAD database, including 19,023 homozygotes. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.12 ( 1273 hom., cov: 30)

Exomes 𝑓: 0.15 ( 17750 hom. )

Consequence

KALRN
NM_001388419.1 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.534

Publications

8 publications found

Variant links:

Genes affected

KALRN (HGNC:4814): (kalirin RhoGEF kinase) Huntington's disease (HD), a neurodegenerative disorder characterized by loss of striatal neurons, is caused by an expansion of a polyglutamine tract in the HD protein huntingtin. This gene encodes a protein that interacts with the huntingtin-associated protein 1, which is a huntingtin binding protein that may function in vesicle trafficking. [provided by RefSeq, Apr 2016]

KALRN links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 3-124395221-G-A is Benign according to our data. Variant chr3-124395221-G-A is described in ClinVar as [Benign]. Clinvar id is 3056443.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=0.534 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.162 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KALRN	NM_001388419.1 link	c.2049G>A	p.Lys683Lys	synonymous_variant	Exon 12 of 60	ENST00000682506.1	NP_001375348.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KALRN	ENST00000682506.1 link	c.2049G>A	p.Lys683Lys	synonymous_variant	Exon 12 of 60		NM_001388419.1	ENSP00000508359.1		A0A804HLI0

Frequencies

GnomAD3 genomes

AF:

0.117

AC:

17657

AN:

150956

Hom.:

1274

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0393

Gnomad AMI

AF:

0.166

Gnomad AMR

AF:

0.133

Gnomad ASJ

AF:

0.129

Gnomad EAS

AF:

0.0215

Gnomad SAS

AF:

0.105

Gnomad FIN

AF:

0.129

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.164

Gnomad OTH

AF:

0.152

GnomAD2 exomes

AF:

0.127

AC:

31693

AN:

250468

AF XY:

0.130

show subpopulations

Gnomad AFR exome

AF:

0.0349

Gnomad AMR exome

AF:

0.109

Gnomad ASJ exome

AF:

0.130

Gnomad EAS exome

AF:

0.0226

Gnomad FIN exome

AF:

0.131

Gnomad NFE exome

AF:

0.164

Gnomad OTH exome

AF:

0.138

GnomAD4 exome

AF:

0.151

AC:

220341

AN:

1461500

Hom.:

17750

Cov.:

AF XY:

0.150

AC XY:

109186

AN XY:

727052

show subpopulations

African (AFR)

AF:

0.0341

AC:

1142

AN:

33474

American (AMR)

AF:

0.113

AC:

5037

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.133

AC:

3483

AN:

26130

East Asian (EAS)

AF:

0.0186

AC:

737

AN:

39692

South Asian (SAS)

AF:

0.112

AC:

9626

AN:

86244

European-Finnish (FIN)

AF:

0.134

AC:

7149

AN:

53398

Middle Eastern (MID)

AF:

0.102

AC:

589

AN:

5766

European-Non Finnish (NFE)

AF:

0.166

AC:

183996

AN:

1111692

Other (OTH)

AF:

0.142

AC:

8582

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

9461

18922

28382

37843

47304

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.117

AC:

17655

AN:

151074

Hom.:

1273

Cov.:

AF XY:

0.115

AC XY:

8488

AN XY:

73716

show subpopulations

African (AFR)

AF:

0.0392

AC:

1615

AN:

41156

American (AMR)

AF:

0.133

AC:

2006

AN:

15054

Ashkenazi Jewish (ASJ)

AF:

0.129

AC:

446

AN:

3464

East Asian (EAS)

AF:

0.0217

AC:

112

AN:

5154

South Asian (SAS)

AF:

0.105

AC:

498

AN:

4742

European-Finnish (FIN)

AF:

0.129

AC:

1337

AN:

10378

Middle Eastern (MID)

AF:

0.0782

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.164

AC:

11154

AN:

67840

Other (OTH)

AF:

0.150

AC:

314

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

752

1504

2256

3008

3760

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.147

Hom.:

1191

Bravo

AF:

0.115

Asia WGS

AF:

0.0810

AC:

281

AN:

3478

EpiCase

AF:

0.162

EpiControl

AF:

0.165

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

KALRN-related disorder

Benign:1

Oct 21, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

6.6

(source)

DANN

Benign

0.62

PhyloP100

0.53

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

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rs9841322

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over