rs3820246

Variant names:

• chr1-245686427-G-A
• rs3820246
• NM_018012.4:c.3444G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_018012.4(KIF26B):​c.3444G>A​(p.Pro1148Pro) 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:3
• Conservation: PhyloP100: -1.65
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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 VariationId is 403008.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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 rank	MANE	Protein	UniProt
KIF26B	NM_018012.4	c.3444G>A	p.Pro1148Pro	synonymous_variant	Exon 12 of 15	ENST00000407071.7	NP_060482.2
LOC105373265	XR_007066988.1	n.657-1976C>T		intron_variant	Intron 3 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIF26B	ENST00000407071.7	c.3444G>A	p.Pro1148Pro	synonymous_variant	Exon 12 of 15	1	NM_018012.4	ENSP00000385545.2
KIF26B	ENST00000366518.4	c.2301G>A	p.Pro767Pro	synonymous_variant	Exon 9 of 12	5		ENSP00000355475.4
KIF26B	ENST00000483253.1	n.1375G>A		non_coding_transcript_exon_variant	Exon 3 of 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

GnomAD2 exomes AF: 0.0488 AC: 12143 AN: 248938 AF XY: 0.0416

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 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

African (AFR) AF: 0.0148 AC: 497 AN: 33480

American (AMR) AF: 0.200 AC: 8930 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00578 AC: 151 AN: 26136

East Asian (EAS) AF: 0.0943 AC: 3743 AN: 39700

South Asian (SAS) AF: 0.0292 AC: 2519 AN: 86258

European-Finnish (FIN) AF: 0.00617 AC: 326 AN: 52808

Middle Eastern (MID) AF: 0.0101 AC: 58 AN: 5768

European-Non Finnish (NFE) AF: 0.0118 AC: 13095 AN: 1111868

Other (OTH) AF: 0.0231 AC: 1393 AN: 60368

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

African (AFR) AF: 0.0160 AC: 665 AN: 41564

American (AMR) AF: 0.105 AC: 1599 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00836 AC: 29 AN: 3470

East Asian (EAS) AF: 0.108 AC: 558 AN: 5164

South Asian (SAS) AF: 0.0346 AC: 167 AN: 4824

European-Finnish (FIN) AF: 0.00386 AC: 41 AN: 10610

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0119 AC: 808 AN: 68000

Other (OTH) AF: 0.0275 AC: 58 AN: 2112

Alfa AF: 0.0201 Hom.: 412

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:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Apr 05, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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). -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.065
DANN	Benign	0.52
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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