3-124219370-C-T

Variant names:

• chr3-124219370-C-T
• rs1444754
• NM_001388419.1:c.74-8620C>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.74-8620C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.543 in 152,026 control chromosomes in the GnomAD database, including 22,822 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 0.54 (22822 hom., cov: 32)
• Consequence: KALRN NM_001388419.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0440
• Publications: 6 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.598 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.74-8620C>T		intron	N/A	NP_001375348.1	O60229-7
	KALRN	NM_001024660.5		c.68-8620C>T		intron	N/A	NP_001019831.2	O60229-1
	KALRN	NM_001322988.2		c.68-8620C>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.74-8620C>T		intron	N/A	ENSP00000508359.1	O60229-7
	KALRN	ENST00000240874.7	TSL:1	c.68-8620C>T		intron	N/A	ENSP00000240874.3	O60229-2
	KALRN	ENST00000460856.5	TSL:1	c.68-8620C>T		intron	N/A	ENSP00000418611.1	C9IZQ6

Frequencies

GnomAD3 genomes AF: 0.543 AC: 82443 AN: 151906 Hom.: 22804 Cov.: 32

Gnomad AFR AF: 0.441

Gnomad AMI AF: 0.564

Gnomad AMR AF: 0.588

Gnomad ASJ AF: 0.618

Gnomad EAS AF: 0.443

Gnomad SAS AF: 0.521

Gnomad FIN AF: 0.515

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.603

Gnomad OTH AF: 0.555

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

GnomAD4 genome AF: 0.543 AC: 82488 AN: 152026 Hom.: 22822 Cov.: 32 AF XY: 0.539 AC XY: 40040 AN XY: 74296

African (AFR) AF: 0.441 AC: 18275 AN: 41442

American (AMR) AF: 0.589 AC: 8999 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.618 AC: 2146 AN: 3470

East Asian (EAS) AF: 0.442 AC: 2283 AN: 5166

South Asian (SAS) AF: 0.521 AC: 2507 AN: 4812

European-Finnish (FIN) AF: 0.515 AC: 5434 AN: 10560

Middle Eastern (MID) AF: 0.602 AC: 177 AN: 294

European-Non Finnish (NFE) AF: 0.603 AC: 40994 AN: 67986

Other (OTH) AF: 0.550 AC: 1159 AN: 2108

Alfa AF: 0.570 Hom.: 7033

Bravo AF: 0.545

Asia WGS AF: 0.478 AC: 1666 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.6
DANN	Benign	0.56
PhyloP100		0.044
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: rs1444754; hg19: chr3-123938217;