rs9289231

Variant names:

• chr3-124055231-T-G
• rs9289231
• NM_001388419.1:c.73+21418T>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001388419.1(KALRN):​c.73+21418T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 152,212 control chromosomes in the GnomAD database, including 2,094 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.14 (2094 hom., cov: 32)
• Consequence: KALRN NM_001388419.1 intron
• Clinical Significance: Benign criteria provided, single submitter P:1 B:2
• Conservation: PhyloP100: 1.02
• Publications: 19 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 3-124055231-T-G is Benign according to our data. Variant chr3-124055231-T-G is described in ClinVar as Benign. ClinVar VariationId is 5458.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001388419.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KALRN	NM_001388419.1	MANE Select	c.73+21418T>G		intron	N/A	NP_001375348.1	O60229-7
	KALRN	NM_001388417.1		c.73+21418T>G		intron	N/A	NP_001375346.1
	KALRN	NM_001388418.1		c.73+21418T>G		intron	N/A	NP_001375347.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KALRN	ENST00000682506.1	MANE Select	c.73+21418T>G		intron	N/A	ENSP00000508359.1	O60229-7
	KALRN	ENST00000683571.1		c.73+21418T>G		intron	N/A	ENSP00000506888.1	A0A804HI42
	KALRN	ENST00000682861.1		c.73+21418T>G		intron	N/A	ENSP00000506756.1	A0A804HHT5

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21594 AN: 152094 Hom.: 2087 Cov.: 32

Gnomad AFR AF: 0.279

Gnomad AMI AF: 0.156

Gnomad AMR AF: 0.0931

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.0115

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.0957

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.0913

Gnomad OTH AF: 0.114

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.142 AC: 21633 AN: 152212 Hom.: 2094 Cov.: 32 AF XY: 0.141 AC XY: 10508 AN XY: 74422

African (AFR) AF: 0.279 AC: 11581 AN: 41494

American (AMR) AF: 0.0929 AC: 1421 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.123 AC: 426 AN: 3470

East Asian (EAS) AF: 0.0112 AC: 58 AN: 5192

South Asian (SAS) AF: 0.104 AC: 500 AN: 4824

European-Finnish (FIN) AF: 0.0957 AC: 1015 AN: 10610

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.0913 AC: 6209 AN: 68004

Other (OTH) AF: 0.114 AC: 241 AN: 2112

Alfa AF: 0.108 Hom.: 3487

Bravo AF: 0.147

Asia WGS AF: 0.0770 AC: 268 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
1	-	1	Coronary heart disease, susceptibility to, 5 (2)
-	-	1	KALRN-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	14
DANN	Benign	0.67
PhyloP100		1.0

Splicing

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

Other links and lift over

dbSNP: rs9289231; hg19: chr3-123774078;