Genetic Variant GIP:c.258-73A>G (chr17-48961892-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.258-73A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.474 in 1,037,598 control chromosomes in the GnomAD database, including 122,403 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.55 ( 25076 hom., cov: 32)

Exomes 𝑓: 0.46 ( 97327 hom. )

Consequence

GIP
NM_004123.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.89

Publications

36 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 (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.791 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GIP	NM_004123.3 link	c.258-73A>G		intron_variant	Intron 3 of 5	ENST00000357424.2	NP_004114.1	P09681

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GIP	ENST00000357424.2 link	c.258-73A>G		intron_variant	Intron 3 of 5	1	NM_004123.3	ENSP00000350005.2		P09681

Frequencies

GnomAD3 genomes

AF:

0.551

AC:

83698

AN:

151904

Hom.:

25022

Cov.:

show subpopulations

Gnomad AFR

AF:

0.797

Gnomad AMI

AF:

0.352

Gnomad AMR

AF:

0.546

Gnomad ASJ

AF:

0.454

Gnomad EAS

AF:

0.287

Gnomad SAS

AF:

0.467

Gnomad FIN

AF:

0.459

Gnomad MID

AF:

0.516

Gnomad NFE

AF:

0.451

Gnomad OTH

AF:

0.532

GnomAD4 exome

AF:

0.461

AC:

408216

AN:

885576

Hom.:

97327

AF XY:

0.459

AC XY:

209922

AN XY:

457798

show subpopulations

African (AFR)

AF:

0.810

AC:

18720

AN:

23098

American (AMR)

AF:

0.537

AC:

19233

AN:

35810

Ashkenazi Jewish (ASJ)

AF:

0.450

AC:

9840

AN:

21866

East Asian (EAS)

AF:

0.272

AC:

9527

AN:

35064

South Asian (SAS)

AF:

0.477

AC:

33338

AN:

69868

European-Finnish (FIN)

AF:

0.462

AC:

17817

AN:

38606

Middle Eastern (MID)

AF:

0.509

AC:

2414

AN:

4740

European-Non Finnish (NFE)

AF:

0.451

AC:

277219

AN:

614846

Other (OTH)

AF:

0.482

AC:

20108

AN:

41678

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.528

Heterozygous variant carriers

10979

21959

32938

43918

54897

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6270

12540

18810

25080

31350

<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:

0.551

AC:

83817

AN:

152022

Hom.:

25076

Cov.:

AF XY:

0.549

AC XY:

40809

AN XY:

74288

show subpopulations

African (AFR)

AF:

0.798

AC:

33094

AN:

41482

American (AMR)

AF:

0.546

AC:

8324

AN:

15246

Ashkenazi Jewish (ASJ)

AF:

0.454

AC:

1577

AN:

3470

East Asian (EAS)

AF:

0.287

AC:

1486

AN:

5170

South Asian (SAS)

AF:

0.468

AC:

2254

AN:

4818

European-Finnish (FIN)

AF:

0.459

AC:

4841

AN:

10558

Middle Eastern (MID)

AF:

0.527

AC:

155

AN:

294

European-Non Finnish (NFE)

AF:

0.451

AC:

30654

AN:

67964

Other (OTH)

AF:

0.527

AC:

1111

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1757

3514

5271

7028

8785

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

690

1380

2070

2760

3450

<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:

0.463

Hom.:

24647

Bravo

AF:

0.566

Asia WGS

AF:

0.432

AC:

1505

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

(source)

DANN

Benign

0.46

PhyloP100

1.9

Mutation Taster

=100/0

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