Variant rs61745397 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001388419.1(KALRN):c.2185T>A(p.Ser729Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00388 in 1,614,082 control chromosomes in the GnomAD database, including 12 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 0.0029 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0040 ( 12 hom. )

Consequence

KALRN
NM_001388419.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.23

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 made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0060512125).

BS2

High AC in GnomAd4 at 444 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KALRN	NM_001388419.1 linkuse as main transcript	c.2185T>A	p.Ser729Thr	missense_variant	13/60	ENST00000682506.1	NP_001375348.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KALRN	ENST00000682506.1 linkuse as main transcript	c.2185T>A	p.Ser729Thr	missense_variant	13/60		NM_001388419.1	ENSP00000508359	A2

Frequencies

GnomAD3 genomes

AF:

0.00292

AC:

444

AN:

152090

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000845

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000786

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0113

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00391

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00266

AC:

669

AN:

251310

Hom.:

AF XY:

0.00248

AC XY:

337

AN XY:

135826

show subpopulations

Gnomad AFR exome

AF:

0.000554

Gnomad AMR exome

AF:

0.000376

Gnomad ASJ exome

AF:

0.00189

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00836

Gnomad NFE exome

AF:

0.00381

Gnomad OTH exome

AF:

0.00228

GnomAD4 exome

AF:

0.00398

AC:

5825

AN:

1461874

Hom.:

Cov.:

AF XY:

0.00373

AC XY:

2710

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.000538

Gnomad4 AMR exome

AF:

0.000470

Gnomad4 ASJ exome

AF:

0.00172

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00829

Gnomad4 NFE exome

AF:

0.00464

Gnomad4 OTH exome

AF:

0.00225

GnomAD4 genome

AF:

0.00292

AC:

444

AN:

152208

Hom.:

Cov.:

AF XY:

0.00310

AC XY:

231

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.000843

Gnomad4 AMR

AF:

0.000785

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0113

Gnomad4 NFE

AF:

0.00391

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00288

Hom.:

Bravo

AF:

0.00202

TwinsUK

AF:

0.00458

AC:

ALSPAC

AF:

0.00597

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00279

AC:

ExAC

AF:

0.00294

AC:

357

EpiCase

AF:

0.00213

EpiControl

AF:

0.00314

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.48

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.020

T;.;T

Eigen

Benign

-0.038

Eigen_PC

Benign

0.080

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.92

D;D;D

M_CAP

Benign

0.029

MetaRNN

Benign

0.0061

T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Uncertain

2.2

.;M;.

MutationTaster

Benign

0.96

D;D;D

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-1.6

N;N;N

REVEL

Benign

0.023

Sift

Benign

0.16

T;T;T

Sift4G

Benign

0.31

T;T;T

Polyphen

0.78

P;P;.

Vest4

0.33

MVP

0.70

MPC

0.59

ClinPred

0.010

GERP RS

4.3

gMVP

0.28

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over