19-45669542-C-A

Variant names:

• chr19-45669542-C-A
• NM_000164.4:c.22C>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000164.4(GIPR):​c.22C>A​(p.Gln8Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000028 in 1,428,526 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 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: not found (cov: 30)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: GIPR NM_000164.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16

Genes affected

GIPR (HGNC:4271): (gastric inhibitory polypeptide receptor) This gene encodes a G-protein coupled receptor for gastric inhibitory polypeptide (GIP), which was originally identified as an activity in gut extracts that inhibited gastric acid secretion and gastrin release, but subsequently was demonstrated to stimulate insulin release in the presence of elevated glucose. Mice lacking this gene exhibit higher blood glucose levels with impaired initial insulin response after oral glucose load. Defect in this gene thus may contribute to the pathogenesis of diabetes. [provided by RefSeq, Oct 2011]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06648156).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GIPR	NM_000164.4	c.22C>A	p.Gln8Lys	missense_variant	Exon 2 of 14	ENST00000590918.6	NP_000155.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GIPR	ENST00000590918.6	c.22C>A	p.Gln8Lys	missense_variant	Exon 2 of 14	1	NM_000164.4	ENSP00000467494.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000280 AC: 4 AN: 1428526 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 707828

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000364

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	2.8
DANN	Benign	0.54
DEOGEN2	Benign	0.10	T;.;.
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.039	N
LIST_S2	Benign	0.50	T;T;T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.066	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L;L;L
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.68	.;N;N
REVEL	Benign	0.044
Sift	Benign	0.14	.;T;T
Sift4G	Benign	0.41	T;T;T
Polyphen		0.0020	B;B;.
Vest4		0.087
MutPred		0.40		Gain of ubiquitination at Q8 (P = 0.0337);Gain of ubiquitination at Q8 (P = 0.0337);Gain of ubiquitination at Q8 (P = 0.0337);
MVP		0.33
MPC		0.74
ClinPred		0.37	T
GERP RS		-7.9
Varity_R		0.097
gMVP		0.61

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-46172800;