rs3820246

chr1-245686427-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_018012.4(KIF26B):c.3444G>A(p.Pro1148=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0215 in 1,613,346 control chromosomes in the GnomAD database, including 1,586 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.026 (176 hom., cov: 33)
  • Exomes 𝑓: 0.021 (1410 hom.)
• Consequence: KIF26B NM_018012.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.65

Genes affected

KIF26B (HGNC:25484): (kinesin family member 26B) The protein encoded by this gene is an intracellular motor protein thought to transport organelles along microtubules. The encoded protein is required for kidney development. Elevated levels of this protein have been found in some breast and colorectal cancers. [provided by RefSeq, Mar 2017]

LOC105373265 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 1-245686427-G-A is Benign according to our data. Variant chr1-245686427-G-A is described in ClinVar as [Benign]. Clinvar id is 403008.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-245686427-G-A is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-1.65 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIF26B	NM_018012.4	c.3444G>A	p.Pro1148=	synonymous_variant	12/15	ENST00000407071.7
LOC105373265	XR_007066988.1	n.657-1976C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIF26B	ENST00000407071.7	c.3444G>A	p.Pro1148=	synonymous_variant	12/15	1	NM_018012.4	A2
KIF26B	ENST00000366518.4	c.2301G>A	p.Pro767=	synonymous_variant	9/12	5		P4
KIF26B	ENST00000483253.1	n.1375G>A		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes AF: 0.0257 AC: 3903 AN: 152116 Hom.: 169 Cov.: 33

Gnomad AFR AF: 0.0156

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.00836

Gnomad EAS AF: 0.108

Gnomad SAS AF: 0.0350

Gnomad FIN AF: 0.00386

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0119

Gnomad OTH AF: 0.0278

GnomAD3 exomes AF: 0.0488 AC: 12143 AN: 248938 Hom.: 1055 AF XY: 0.0416 AC XY: 5626 AN XY: 135198

Gnomad AFR exome AF: 0.0149

Gnomad AMR exome AF: 0.211

Gnomad ASJ exome AF: 0.00577

Gnomad EAS exome AF: 0.116

Gnomad SAS exome AF: 0.0304

Gnomad FIN exome AF: 0.00557

Gnomad NFE exome AF: 0.0108

Gnomad OTH exome AF: 0.0365

GnomAD4 exome AF: 0.0210 AC: 30712 AN: 1461110 Hom.: 1410 Cov.: 51 AF XY: 0.0203 AC XY: 14777 AN XY: 726860

Gnomad4 AFR exome AF: 0.0148

Gnomad4 AMR exome AF: 0.200

Gnomad4 ASJ exome AF: 0.00578

Gnomad4 EAS exome AF: 0.0943

Gnomad4 SAS exome AF: 0.0292

Gnomad4 FIN exome AF: 0.00617

Gnomad4 NFE exome AF: 0.0118

Gnomad4 OTH exome AF: 0.0231

GnomAD4 genome AF: 0.0258 AC: 3932 AN: 152236 Hom.: 176 Cov.: 33 AF XY: 0.0277 AC XY: 2063 AN XY: 74428

Gnomad4 AFR AF: 0.0160

Gnomad4 AMR AF: 0.105

Gnomad4 ASJ AF: 0.00836

Gnomad4 EAS AF: 0.108

Gnomad4 SAS AF: 0.0346

Gnomad4 FIN AF: 0.00386

Gnomad4 NFE AF: 0.0119

Gnomad4 OTH AF: 0.0275

Alfa AF: 0.0186 Hom.: 181

Bravo AF: 0.0350

Asia WGS AF: 0.0740 AC: 257 AN: 3478

EpiCase AF: 0.0110

EpiControl AF: 0.00966

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

KIF26B-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 05, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.065
Dann	Benign	0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs3820246; hg19: chr1-245849729; COSMIC: COSV63638699;