3-124581410-C-T

Variant names:

• chr3-124581410-C-T
• rs2010099
• NM_001388419.1:c.5182+18321C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001388419.1(KALRN):​c.5182+18321C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 141,652 control chromosomes in the GnomAD database, including 739 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 0.10 (739 hom., cov: 30)
• Consequence: KALRN NM_001388419.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.107
• Publications: 12 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]

LOC105374076 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.12 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.5182+18321C>T		intron	N/A	NP_001375348.1	O60229-7
	KALRN	NM_001024660.5		c.5176+18321C>T		intron	N/A	NP_001019831.2	O60229-1
	KALRN	NM_001322988.2		c.5176+18321C>T		intron	N/A	NP_001309917.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KALRN	ENST00000682506.1	MANE Select	c.5182+18321C>T		intron	N/A	ENSP00000508359.1	O60229-7
	KALRN	ENST00000360013.7	TSL:5	c.5176+18321C>T		intron	N/A	ENSP00000353109.3	O60229-1
	KALRN	ENST00000354186.8	TSL:5	c.5080+18321C>T		intron	N/A	ENSP00000346122.4	H7BXZ5

Frequencies

GnomAD3 genomes AF: 0.101 AC: 14257 AN: 141620 Hom.: 740 Cov.: 30

Gnomad AFR AF: 0.0882

Gnomad AMI AF: 0.0644

Gnomad AMR AF: 0.0894

Gnomad ASJ AF: 0.0614

Gnomad EAS AF: 0.0755

Gnomad SAS AF: 0.0640

Gnomad FIN AF: 0.0599

Gnomad MID AF: 0.113

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.117

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

GnomAD4 genome AF: 0.101 AC: 14259 AN: 141652 Hom.: 739 Cov.: 30 AF XY: 0.0966 AC XY: 6628 AN XY: 68598

African (AFR) AF: 0.0882 AC: 3412 AN: 38678

American (AMR) AF: 0.0893 AC: 1242 AN: 13906

Ashkenazi Jewish (ASJ) AF: 0.0614 AC: 203 AN: 3308

East Asian (EAS) AF: 0.0750 AC: 356 AN: 4744

South Asian (SAS) AF: 0.0640 AC: 287 AN: 4482

European-Finnish (FIN) AF: 0.0599 AC: 535 AN: 8926

Middle Eastern (MID) AF: 0.104 AC: 28 AN: 268

European-Non Finnish (NFE) AF: 0.123 AC: 7913 AN: 64536

Other (OTH) AF: 0.117 AC: 227 AN: 1934

Alfa AF: 0.107 Hom.: 2102

Bravo AF: 0.0968

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	10
DANN	Benign	0.92
PhyloP100		0.11
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs2010099; hg19: chr3-124300257;