dbSNP rs777093189: GKN1:c.-17G>A (chr2-68974661-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_019617.4(GKN1):c.-17G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000355 in 1,605,230 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000035 ( 1 hom. )

Consequence

GKN1
NM_019617.4 5_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.208

Publications

0 publications found

Variant links:

Genes affected

GKN1 (HGNC:23217): (gastrokine 1) The protein encoded by this gene is found to be down-regulated in human gastric cancer tissue as compared to normal gastric mucosa. [provided by RefSeq, Jul 2008]

GKN1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08760944).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019617.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GKN1	NM_019617.4	MANE Select	c.-17G>A		5_prime_UTR	Exon 1 of 6	NP_062563.4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GKN1	ENST00000377938.4	TSL:1 MANE Select	c.-17G>A		5_prime_UTR	Exon 1 of 6	ENSP00000367172.3	Q9NS71
GKN1	ENST00000673932.3		c.26G>A	p.Cys9Tyr	missense	Exon 1 of 6	ENSP00000501093.2	A0A8I5KHR1
GKN1	ENST00000478888.1	TSL:2	n.26G>A		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000199

AC:

AN:

251252

AF XY:

0.0000147

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000440

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000351

AC:

AN:

1453062

Hom.:

Cov.:

AF XY:

0.0000401

AC XY:

AN XY:

723390

show subpopulations

African (AFR)

AF:

0.0000301

AC:

AN:

33256

American (AMR)

AF:

0.00

AC:

AN:

44700

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26070

East Asian (EAS)

AF:

0.00

AC:

AN:

39646

South Asian (SAS)

AF:

0.00

AC:

AN:

86082

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.0000444

AC:

AN:

1104022

Other (OTH)

AF:

0.0000166

AC:

AN:

60116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152168

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41436

American (AMR)

AF:

0.00

AC:

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5202

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

68028

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000772

Hom.:

Bravo

AF:

0.0000416

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.0000546

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.54

CADD

Benign

5.4

(source)

DANN

Benign

0.37

DEOGEN2

Benign

0.051

Eigen

Benign

-0.97

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.022

LIST_S2

Benign

0.42

M_CAP

Benign

0.0075

MetaRNN

Benign

0.088

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

PhyloP100

0.21

PrimateAI

Benign

0.37

PROVEAN

Benign

-1.1

REVEL

Benign

0.021

Sift

Uncertain

0.0090

Sift4G

Pathogenic

0.0

Polyphen

0.030

Vest4

0.33

MVP

0.45

MPC

0.42

ClinPred

0.065

GERP RS

0.019

PromoterAI

-0.013

Neutral

(source)

Varity_R

0.098

gMVP

0.58

Mutation Taster

=98/2

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over