rs1867647

Variant names:

• chr3-124517982-T-C
• rs1867647
• NM_001388419.1:c.4935+21569T>C

Variant summary

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

The NM_001388419.1(KALRN):​c.4935+21569T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.551 in 152,100 control chromosomes in the GnomAD database, including 24,275 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 0.55 (24275 hom., cov: 32)
• Consequence: KALRN NM_001388419.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0790
• Publications: 2 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]

ENSG00000297494 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.726 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.4935+21569T>C		intron	N/A	NP_001375348.1	O60229-7
	KALRN	NM_001024660.5		c.4929+21569T>C		intron	N/A	NP_001019831.2	O60229-1
	KALRN	NM_001322988.2		c.4929+21569T>C		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.4935+21569T>C		intron	N/A	ENSP00000508359.1	O60229-7
	KALRN	ENST00000240874.7	TSL:1	c.4930-418T>C		intron	N/A	ENSP00000240874.3	O60229-2
	KALRN	ENST00000460856.5	TSL:1	c.4903-418T>C		intron	N/A	ENSP00000418611.1	C9IZQ6

Frequencies

GnomAD3 genomes AF: 0.551 AC: 83725 AN: 151982 Hom.: 24233 Cov.: 32

Gnomad AFR AF: 0.733

Gnomad AMI AF: 0.589

Gnomad AMR AF: 0.485

Gnomad ASJ AF: 0.532

Gnomad EAS AF: 0.379

Gnomad SAS AF: 0.574

Gnomad FIN AF: 0.371

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.494

Gnomad OTH AF: 0.557

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

GnomAD4 genome AF: 0.551 AC: 83811 AN: 152100 Hom.: 24275 Cov.: 32 AF XY: 0.544 AC XY: 40431 AN XY: 74362

African (AFR) AF: 0.733 AC: 30440 AN: 41506

American (AMR) AF: 0.484 AC: 7404 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.532 AC: 1848 AN: 3472

East Asian (EAS) AF: 0.379 AC: 1958 AN: 5164

South Asian (SAS) AF: 0.575 AC: 2768 AN: 4818

European-Finnish (FIN) AF: 0.371 AC: 3922 AN: 10574

Middle Eastern (MID) AF: 0.586 AC: 171 AN: 292

European-Non Finnish (NFE) AF: 0.494 AC: 33593 AN: 67962

Other (OTH) AF: 0.554 AC: 1171 AN: 2114

Alfa AF: 0.522 Hom.: 27151

Bravo AF: 0.570

Asia WGS AF: 0.514 AC: 1788 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	5.0
DANN	Benign	0.39
PhyloP100		-0.079
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: rs1867647; hg19: chr3-124236829; COSMIC: COSV53758042;