dbSNP rs2289420: KALRN:p.Val2205Val (chr3-124667095-T-C) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_001388419.1(KALRN):c.6615T>C(p.Val2205Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0274 in 1,613,910 control chromosomes in the GnomAD database, including 834 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 0.028 ( 81 hom., cov: 32)

Exomes 𝑓: 0.027 ( 753 hom. )

Consequence

KALRN
NM_001388419.1 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0870

Publications

7 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.041).

BP7

Synonymous conserved (PhyloP=-0.087 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0725 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KALRN	NM_001388419.1 link	c.6615T>C	p.Val2205Val	synonymous_variant	Exon 47 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.6615T>C	p.Val2205Val	synonymous_variant	Exon 47 of 60		NM_001388419.1	ENSP00000508359.1		A0A804HLI0

Frequencies

GnomAD3 genomes

AF:

0.0277

AC:

4222

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0274

Gnomad AMI

AF:

0.0164

Gnomad AMR

AF:

0.0401

Gnomad ASJ

AF:

0.0216

Gnomad EAS

AF:

0.0784

Gnomad SAS

AF:

0.0456

Gnomad FIN

AF:

0.00847

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0237

Gnomad OTH

AF:

0.0220

GnomAD2 exomes

AF:

0.0318

AC:

7986

AN:

251264

AF XY:

0.0313

show subpopulations

Gnomad AFR exome

AF:

0.0257

Gnomad AMR exome

AF:

0.0482

Gnomad ASJ exome

AF:

0.0185

Gnomad EAS exome

AF:

0.0891

Gnomad FIN exome

AF:

0.00776

Gnomad NFE exome

AF:

0.0214

Gnomad OTH exome

AF:

0.0279

GnomAD4 exome

AF:

0.0273

AC:

39941

AN:

1461584

Hom.:

753

Cov.:

AF XY:

0.0274

AC XY:

19912

AN XY:

727086

show subpopulations

African (AFR)

AF:

0.0261

AC:

873

AN:

33472

American (AMR)

AF:

0.0496

AC:

2218

AN:

44698

Ashkenazi Jewish (ASJ)

AF:

0.0168

AC:

438

AN:

26134

East Asian (EAS)

AF:

0.0956

AC:

3793

AN:

39676

South Asian (SAS)

AF:

0.0438

AC:

3776

AN:

86162

European-Finnish (FIN)

AF:

0.00837

AC:

447

AN:

53416

Middle Eastern (MID)

AF:

0.0121

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0238

AC:

26455

AN:

1111870

Other (OTH)

AF:

0.0310

AC:

1871

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.439

Heterozygous variant carriers

1915

3830

5744

7659

9574

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1106

2212

3318

4424

5530

<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:

0.0278

AC:

4241

AN:

152326

Hom.:

Cov.:

AF XY:

0.0280

AC XY:

2089

AN XY:

74490

show subpopulations

African (AFR)

AF:

0.0274

AC:

1140

AN:

41582

American (AMR)

AF:

0.0406

AC:

621

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0216

AC:

AN:

3472

East Asian (EAS)

AF:

0.0788

AC:

408

AN:

5180

South Asian (SAS)

AF:

0.0460

AC:

222

AN:

4824

European-Finnish (FIN)

AF:

0.00847

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0237

AC:

1612

AN:

68024

Other (OTH)

AF:

0.0241

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

209

417

626

834

1043

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

150

200

250

<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:

0.0243

Hom.:

Bravo

AF:

0.0299

Asia WGS

AF:

0.0560

AC:

194

AN:

3478

EpiCase

AF:

0.0236

EpiControl

AF:

0.0202

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

5.8

(source)

DANN

Benign

0.74

PhyloP100

-0.087

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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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