Genetic Variant NM_004123.3:c.307A>G (chr17-48961770-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004123.3(GIP):c.307A>G(p.Ser103Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.506 in 1,610,816 control chromosomes in the GnomAD database, including 213,936 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.41 ( 15132 hom., cov: 31)

Exomes 𝑓: 0.52 ( 198804 hom. )

Consequence

GIP
NM_004123.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0500

Publications

85 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.907024E-6).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.687 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GIP	NM_004123.3 link	c.307A>G	p.Ser103Gly	missense_variant	Exon 4 of 6	ENST00000357424.2	NP_004114.1	P09681

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GIP	ENST00000357424.2 link	c.307A>G	p.Ser103Gly	missense_variant	Exon 4 of 6	1	NM_004123.3	ENSP00000350005.2		P09681

Frequencies

GnomAD3 genomes

AF:

0.409

AC:

62177

AN:

151920

Hom.:

15139

Cov.:

show subpopulations

Gnomad AFR

AF:

0.136

Gnomad AMI

AF:

0.584

Gnomad AMR

AF:

0.412

Gnomad ASJ

AF:

0.518

Gnomad EAS

AF:

0.707

Gnomad SAS

AF:

0.506

Gnomad FIN

AF:

0.516

Gnomad MID

AF:

0.462

Gnomad NFE

AF:

0.520

Gnomad OTH

AF:

0.436

GnomAD2 exomes

AF:

0.496

AC:

123525

AN:

249106

AF XY:

0.505

show subpopulations

Gnomad AFR exome

AF:

0.126

Gnomad AMR exome

AF:

0.435

Gnomad ASJ exome

AF:

0.526

Gnomad EAS exome

AF:

0.705

Gnomad FIN exome

AF:

0.520

Gnomad NFE exome

AF:

0.526

Gnomad OTH exome

AF:

0.512

GnomAD4 exome

AF:

0.516

AC:

752581

AN:

1458778

Hom.:

198804

Cov.:

AF XY:

0.517

AC XY:

375515

AN XY:

725890

show subpopulations

African (AFR)

AF:

0.116

AC:

3895

AN:

33466

American (AMR)

AF:

0.435

AC:

19426

AN:

44630

Ashkenazi Jewish (ASJ)

AF:

0.525

AC:

13711

AN:

26106

East Asian (EAS)

AF:

0.718

AC:

28495

AN:

39678

South Asian (SAS)

AF:

0.491

AC:

42355

AN:

86194

European-Finnish (FIN)

AF:

0.516

AC:

27030

AN:

52346

Middle Eastern (MID)

AF:

0.470

AC:

2708

AN:

5764

European-Non Finnish (NFE)

AF:

0.527

AC:

585344

AN:

1110280

Other (OTH)

AF:

0.491

AC:

29617

AN:

60314

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

16511

33021

49532

66042

82553

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16642

33284

49926

66568

83210

<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:

0.409

AC:

62164

AN:

152038

Hom.:

15132

Cov.:

AF XY:

0.411

AC XY:

30544

AN XY:

74298

show subpopulations

African (AFR)

AF:

0.135

AC:

5622

AN:

41512

American (AMR)

AF:

0.412

AC:

6285

AN:

15250

Ashkenazi Jewish (ASJ)

AF:

0.518

AC:

1797

AN:

3468

East Asian (EAS)

AF:

0.706

AC:

3637

AN:

5150

South Asian (SAS)

AF:

0.506

AC:

2442

AN:

4830

European-Finnish (FIN)

AF:

0.516

AC:

5440

AN:

10552

Middle Eastern (MID)

AF:

0.456

AC:

134

AN:

294

European-Non Finnish (NFE)

AF:

0.520

AC:

35346

AN:

67958

Other (OTH)

AF:

0.440

AC:

930

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1652

3303

4955

6606

8258

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

586

1172

1758

2344

2930

<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:

0.491

Hom.:

59808

Bravo

AF:

0.393

TwinsUK

AF:

0.522

AC:

1937

ALSPAC

AF:

0.510

AC:

1967

ESP6500AA

AF:

0.143

AC:

628

ESP6500EA

AF:

0.535

AC:

4604

ExAC

AF:

0.490

AC:

59534

Asia WGS

AF:

0.547

AC:

1898

AN:

3476

EpiCase

AF:

0.523

EpiControl

AF:

0.528

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.81

BayesDel_noAF

Benign

-0.80

CADD

Benign

3.7

(source)

DANN

Benign

0.34

DEOGEN2

Benign

0.20

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.019

LIST_S2

Benign

0.40

MetaRNN

Benign

0.0000019

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-0.12

PhyloP100

0.050

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.14

REVEL

Benign

0.027

Sift

Benign

0.77

Sift4G

Benign

0.63

Polyphen

0.0

Vest4

0.0020

MPC

0.022

ClinPred

0.0052

GERP RS

-5.1

Varity_R

0.035

gMVP

0.039

Mutation Taster

=97/3

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over