Genetic Variant GIP:p.Cys148Tyr (chr17-48960895-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_004123.3(GIP):c.443G>A(p.Cys148Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000621 in 1,594,106 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00033 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000033 ( 0 hom. )

Consequence

GIP
NM_004123.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.531

Publications

0 publications found

Variant links:

Genes affected

GIP (HGNC:4270): (gastric inhibitory polypeptide) This gene encodes an incretin hormone and belongs to the glucagon superfamily. The encoded protein is important in maintaining glucose homeostasis as it is a potent stimulator of insulin secretion from pancreatic beta-cells following food ingestion and nutrient absorption. This gene stimulates insulin secretion via its G protein-coupled receptor activation of adenylyl cyclase and other signal transduction pathways. It is a relatively poor inhibitor of gastric acid secretion. [provided by RefSeq, Jul 2008]

GIP links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.04164061).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004123.3. 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
	GIP	NM_004123.3	MANE Select	c.443G>A	p.Cys148Tyr	missense	Exon 5 of 6	NP_004114.1	P09681

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GIP	ENST00000357424.2	TSL:1 MANE Select	c.443G>A	p.Cys148Tyr	missense	Exon 5 of 6	ENSP00000350005.2	P09681

Frequencies

GnomAD3 genomes

AF:

0.000335

AC:

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00116

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

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:

0.00

Gnomad OTH

AF:

0.000956

GnomAD2 exomes

AF:

0.0000744

AC:

AN:

228566

AF XY:

0.0000652

show subpopulations

Gnomad AFR exome

AF:

0.000910

Gnomad AMR exome

AF:

0.000125

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000333

AC:

AN:

1441852

Hom.:

Cov.:

AF XY:

0.0000293

AC XY:

AN XY:

715862

show subpopulations

African (AFR)

AF:

0.00117

AC:

AN:

33256

American (AMR)

AF:

0.000142

AC:

AN:

42362

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25684

East Asian (EAS)

AF:

0.00

AC:

AN:

39376

South Asian (SAS)

AF:

0.00

AC:

AN:

83086

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52502

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5740

European-Non Finnish (NFE)

AF:

9.09e-7

AC:

AN:

1100096

Other (OTH)

AF:

0.0000335

AC:

AN:

59750

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.436

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.000335

AC:

AN:

152254

Hom.:

Cov.:

AF XY:

0.000390

AC XY:

AN XY:

74442

show subpopulations

African (AFR)

AF:

0.00116

AC:

AN:

41550

American (AMR)

AF:

0.0000655

AC:

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68030

Other (OTH)

AF:

0.000946

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.523

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:

0.0000852

Hom.:

Bravo

AF:

0.000336

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000659

AC:

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

0.16

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Benign

0.81

DEOGEN2

Uncertain

0.64

Eigen

Benign

-0.75

Eigen_PC

Benign

-0.72

FATHMM_MKL

Benign

0.073

LIST_S2

Benign

0.49

M_CAP

Benign

0.0043

MetaRNN

Benign

0.042

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

PhyloP100

0.53

PrimateAI

Uncertain

0.50

PROVEAN

Pathogenic

-6.0

REVEL

Benign

0.059

Sift

Uncertain

0.0020

Sift4G

Benign

0.19

Polyphen

0.0050

Vest4

0.33

MVP

0.15

MPC

0.031

ClinPred

0.061

GERP RS

2.5

Varity_R

0.46

gMVP

0.18

Mutation Taster

=92/8

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