chr1-245687987-G-T

Variant names:

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

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.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
• Publications: 3 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=-0.88).
• BP6: Variant 1-245687987-G-T is Benign according to our data. Variant chr1-245687987-G-T is described in ClinVar as Benign. ClinVar VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018012.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF26B	NM_018012.4	MANE Select	c.5004G>T	p.Ser1668Ser	synonymous	Exon 12 of 15	NP_060482.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF26B	ENST00000407071.7	TSL:1 MANE Select	c.5004G>T	p.Ser1668Ser	synonymous	Exon 12 of 15	ENSP00000385545.2
	KIF26B	ENST00000366518.4	TSL:5	c.3861G>T	p.Ser1287Ser	synonymous	Exon 9 of 12	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

GnomAD2 exomes AF: 0.0541 AC: 9511 AN: 175710 AF XY: 0.0470

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 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

African (AFR) AF: 0.00388 AC: 126 AN: 32470

American (AMR) AF: 0.190 AC: 7376 AN: 38732

Ashkenazi Jewish (ASJ) AF: 0.00467 AC: 119 AN: 25478

East Asian (EAS) AF: 0.0972 AC: 3608 AN: 37110

South Asian (SAS) AF: 0.0429 AC: 3472 AN: 80992

European-Finnish (FIN) AF: 0.00597 AC: 291 AN: 48748

Middle Eastern (MID) AF: 0.0106 AC: 61 AN: 5728

European-Non Finnish (NFE) AF: 0.0123 AC: 13410 AN: 1093978

Other (OTH) AF: 0.0232 AC: 1370 AN: 58960

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

African (AFR) AF: 0.00577 AC: 240 AN: 41594

American (AMR) AF: 0.103 AC: 1581 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00662 AC: 23 AN: 3472

East Asian (EAS) AF: 0.113 AC: 580 AN: 5152

South Asian (SAS) AF: 0.0512 AC: 247 AN: 4828

European-Finnish (FIN) AF: 0.00386 AC: 41 AN: 10630

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0122 AC: 829 AN: 68014

Other (OTH) AF: 0.0256 AC: 54 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.032
DANN	Benign	0.63
PhyloP100		-3.1
Mutation Taster		=72/28	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: rs58427858; hg19: chr1-245851289;