chr17-48961892-T-C

Position:

• chr17-48961892-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.89

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
GIP	NM_004123.3	c.258-73A>G		intron_variant		ENST00000357424.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GIP	ENST00000357424.2	c.258-73A>G		intron_variant		1	NM_004123.3	P1

Frequencies

GnomAD3 genomes AF: 0.551 AC: 83698 AN: 151904 Hom.: 25022 Cov.: 32

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

Gnomad4 AFR exome AF: 0.810

Gnomad4 AMR exome AF: 0.537

Gnomad4 ASJ exome AF: 0.450

Gnomad4 EAS exome AF: 0.272

Gnomad4 SAS exome AF: 0.477

Gnomad4 FIN exome AF: 0.462

Gnomad4 NFE exome AF: 0.451

Gnomad4 OTH exome AF: 0.482

GnomAD4 genome AF: 0.551 AC: 83817 AN: 152022 Hom.: 25076 Cov.: 32 AF XY: 0.549 AC XY: 40809 AN XY: 74288

Gnomad4 AFR AF: 0.798

Gnomad4 AMR AF: 0.546

Gnomad4 ASJ AF: 0.454

Gnomad4 EAS AF: 0.287

Gnomad4 SAS AF: 0.468

Gnomad4 FIN AF: 0.459

Gnomad4 NFE AF: 0.451

Gnomad4 OTH AF: 0.527

Alfa AF: 0.461 Hom.: 18071

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	13
DANN	Benign	0.46

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

LitVar

Other links and lift over

dbSNP: rs2291726; hg19: chr17-47039254; COSMIC: COSV62468073;