rs2291726

Variant names:

• chr17-48961892-T-A
• rs2291726
• NM_004123.3:c.258-73A>T

Your query was ambiguous. Multiple possible variants found:

• chr17-48961892-T-A
• chr17-48961892-T-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004123.3(GIP):​c.258-73A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GIP NM_004123.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.89
• Publications: 36 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 887142 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 458574

African (AFR) AF: 0.00 AC: 0 AN: 23112

American (AMR) AF: 0.00 AC: 0 AN: 35820

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21878

East Asian (EAS) AF: 0.00 AC: 0 AN: 35090

South Asian (SAS) AF: 0.00 AC: 0 AN: 69918

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38636

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4740

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 616222

Other (OTH) AF: 0.00 AC: 0 AN: 41726

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 24647

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	13
DANN	Benign	0.46
PhyloP100		1.9

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2291726; hg19: chr17-47039254;