chr3-124240738-T-C

Variant names:

• chr3-124240738-T-C
• rs7616435
• NM_001388419.1:c.263+5795T>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.263+5795T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 152,138 control chromosomes in the GnomAD database, including 1,891 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 0.13 (1891 hom., cov: 32)
• Consequence: KALRN NM_001388419.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.468
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.27 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.263+5795T>C		intron	N/A	NP_001375348.1	O60229-7
	KALRN	NM_001024660.5		c.257+5795T>C		intron	N/A	NP_001019831.2	O60229-1
	KALRN	NM_001322988.2		c.257+5795T>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.263+5795T>C		intron	N/A	ENSP00000508359.1	O60229-7
	KALRN	ENST00000240874.7	TSL:1	c.257+5795T>C		intron	N/A	ENSP00000240874.3	O60229-2
	KALRN	ENST00000460856.5	TSL:1	c.257+5795T>C		intron	N/A	ENSP00000418611.1	C9IZQ6

Frequencies

GnomAD3 genomes AF: 0.125 AC: 19026 AN: 152018 Hom.: 1884 Cov.: 32

Gnomad AFR AF: 0.274

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.0874

Gnomad ASJ AF: 0.0879

Gnomad EAS AF: 0.0886

Gnomad SAS AF: 0.0773

Gnomad FIN AF: 0.0783

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.0583

Gnomad OTH AF: 0.126

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

GnomAD4 genome AF: 0.125 AC: 19061 AN: 152138 Hom.: 1891 Cov.: 32 AF XY: 0.125 AC XY: 9305 AN XY: 74368

African (AFR) AF: 0.274 AC: 11366 AN: 41490

American (AMR) AF: 0.0872 AC: 1333 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0879 AC: 305 AN: 3470

East Asian (EAS) AF: 0.0888 AC: 460 AN: 5180

South Asian (SAS) AF: 0.0767 AC: 368 AN: 4796

European-Finnish (FIN) AF: 0.0783 AC: 830 AN: 10600

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.0582 AC: 3961 AN: 68002

Other (OTH) AF: 0.127 AC: 267 AN: 2110

Alfa AF: 0.0850 Hom.: 1103

Bravo AF: 0.132

Asia WGS AF: 0.101 AC: 351 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	11
DANN	Benign	0.85
PhyloP100		0.47
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: rs7616435; hg19: chr3-123959585;