1-245687987-G-T

Variant names:

• chr1-245687987-G-T
• rs58427858
• NM_018012.4:c.5004G>T

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.5004G>T​(p.Ser1668Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0212 in 1,574,508 control chromosomes in the GnomAD database, including 1,408 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.024 (180 hom., cov: 33)
  • Exomes 𝑓: 0.021 (1228 hom.)
• Consequence: KIF26B NM_018012.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -3.07

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=-0.88).
• BP6: Variant 1-245687987-G-T is Benign according to our data. Variant chr1-245687987-G-T is described in ClinVar as [Benign]. Clinvar id is 403010.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.07 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF26B	NM_018012.4	c.5004G>T	p.Ser1668Ser	synonymous_variant	Exon 12 of 15	ENST00000407071.7	NP_060482.2
LOC105373265	XR_007066988.1	n.657-3536C>A		intron_variant	Intron 3 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIF26B	ENST00000407071.7	c.5004G>T	p.Ser1668Ser	synonymous_variant	Exon 12 of 15	1	NM_018012.4	ENSP00000385545.2
KIF26B	ENST00000366518.4	c.3861G>T	p.Ser1287Ser	synonymous_variant	Exon 9 of 12	5		ENSP00000355475.4

Frequencies

GnomAD3 genomes AF: 0.0236 AC: 3591 AN: 152194 Hom.: 177 Cov.: 33

Gnomad AFR AF: 0.00579

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.00662

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.0515

Gnomad FIN AF: 0.00386

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0122

Gnomad OTH AF: 0.0254

GnomAD3 exomes AF: 0.0541 AC: 9511 AN: 175710 Hom.: 810 AF XY: 0.0470 AC XY: 4506 AN XY: 95820

Gnomad AFR exome AF: 0.00443

Gnomad AMR exome AF: 0.205

Gnomad ASJ exome AF: 0.00450

Gnomad EAS exome AF: 0.126

Gnomad SAS exome AF: 0.0456

Gnomad FIN exome AF: 0.00525

Gnomad NFE exome AF: 0.0117

Gnomad OTH exome AF: 0.0378

GnomAD4 exome AF: 0.0210 AC: 29833 AN: 1422196 Hom.: 1228 Cov.: 69 AF XY: 0.0209 AC XY: 14697 AN XY: 703834

Gnomad4 AFR exome AF: 0.00388

Gnomad4 AMR exome AF: 0.190

Gnomad4 ASJ exome AF: 0.00467

Gnomad4 EAS exome AF: 0.0972

Gnomad4 SAS exome AF: 0.0429

Gnomad4 FIN exome AF: 0.00597

Gnomad4 NFE exome AF: 0.0123

Gnomad4 OTH exome AF: 0.0232

GnomAD4 genome AF: 0.0236 AC: 3601 AN: 152312 Hom.: 180 Cov.: 33 AF XY: 0.0257 AC XY: 1913 AN XY: 74464

Gnomad4 AFR AF: 0.00577

Gnomad4 AMR AF: 0.103

Gnomad4 ASJ AF: 0.00662

Gnomad4 EAS AF: 0.113

Gnomad4 SAS AF: 0.0512

Gnomad4 FIN AF: 0.00386

Gnomad4 NFE AF: 0.0122

Gnomad4 OTH AF: 0.0256

Alfa AF: 0.0100 Hom.: 9

Bravo AF: 0.0326

Asia WGS AF: 0.0810 AC: 283 AN: 3478

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	-0.88
CADD	Benign	0.032
DANN	Benign	0.63

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: rs58427858; hg19: chr1-245851289;