1-245687204-G-C

Variant names:

• chr1-245687204-G-C
• rs3806273
• NM_018012.4:c.4221G>C

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.4221G>C​(p.Pro1407Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0334 in 1,612,438 control chromosomes in the GnomAD database, including 2,300 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.056 (440 hom., cov: 32)
  • Exomes 𝑓: 0.031 (1860 hom.)
• Consequence: KIF26B NM_018012.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -2.91
• 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=-0.93).
• BP6: Variant 1-245687204-G-C is Benign according to our data. Variant chr1-245687204-G-C is described in ClinVar as Benign. ClinVar VariationId is 403009.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.91 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF26B	NM_018012.4	c.4221G>C	p.Pro1407Pro	synonymous_variant	Exon 12 of 15	ENST00000407071.7	NP_060482.2
LOC105373265	XR_007066988.1	n.657-2753C>G		intron_variant	Intron 3 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIF26B	ENST00000407071.7	c.4221G>C	p.Pro1407Pro	synonymous_variant	Exon 12 of 15	1	NM_018012.4	ENSP00000385545.2
KIF26B	ENST00000366518.4	c.3078G>C	p.Pro1026Pro	synonymous_variant	Exon 9 of 12	5		ENSP00000355475.4
KIF26B	ENST00000483253.1	n.2152G>C		non_coding_transcript_exon_variant	Exon 3 of 3	2

Frequencies

GnomAD3 genomes AF: 0.0561 AC: 8519 AN: 151924 Hom.: 423 Cov.: 32

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.00837

Gnomad EAS AF: 0.109

Gnomad SAS AF: 0.0414

Gnomad FIN AF: 0.00520

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0202

Gnomad OTH AF: 0.0541

GnomAD2 exomes AF: 0.0596 AC: 14623 AN: 245464 AF XY: 0.0506

Gnomad AFR exome AF: 0.110

Gnomad AMR exome AF: 0.217

Gnomad ASJ exome AF: 0.00514

Gnomad EAS exome AF: 0.116

Gnomad FIN exome AF: 0.00667

Gnomad NFE exome AF: 0.0178

Gnomad OTH exome AF: 0.0443

GnomAD4 exome AF: 0.0310 AC: 45250 AN: 1460396 Hom.: 1860 Cov.: 57 AF XY: 0.0301 AC XY: 21848 AN XY: 726368

African (AFR) AF: 0.107 AC: 3577 AN: 33472

American (AMR) AF: 0.207 AC: 9224 AN: 44522

Ashkenazi Jewish (ASJ) AF: 0.00567 AC: 148 AN: 26110

East Asian (EAS) AF: 0.0945 AC: 3750 AN: 39670

South Asian (SAS) AF: 0.0348 AC: 2999 AN: 86056

European-Finnish (FIN) AF: 0.00790 AC: 418 AN: 52894

Middle Eastern (MID) AF: 0.0196 AC: 113 AN: 5758

European-Non Finnish (NFE) AF: 0.0205 AC: 22783 AN: 1111568

Other (OTH) AF: 0.0371 AC: 2238 AN: 60346

GnomAD4 genome AF: 0.0565 AC: 8585 AN: 152042 Hom.: 440 Cov.: 32 AF XY: 0.0577 AC XY: 4284 AN XY: 74294

African (AFR) AF: 0.107 AC: 4431 AN: 41462

American (AMR) AF: 0.119 AC: 1818 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00837 AC: 29 AN: 3466

East Asian (EAS) AF: 0.109 AC: 561 AN: 5154

South Asian (SAS) AF: 0.0412 AC: 198 AN: 4806

European-Finnish (FIN) AF: 0.00520 AC: 55 AN: 10580

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0202 AC: 1371 AN: 67982

Other (OTH) AF: 0.0535 AC: 113 AN: 2112

Alfa AF: 0.0112 Hom.: 6

Bravo AF: 0.0695

Asia WGS AF: 0.0860 AC: 301 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

Oct 28, 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	-0.93
CADD	Benign	0.0010
DANN	Benign	0.57
PhyloP100		-2.9
Mutation Taster		=97/3	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: rs3806273; hg19: chr1-245850506; COSMIC: COSV63638037;