12-122842051-G-T

Position:

• chr12-122842051-G-T

Variant summary

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

The NM_003959.3(HIP1R):​c.94-5980G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.286 in 152,058 control chromosomes in the GnomAD database, including 7,355 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 0.29 (7355 hom., cov: 32)
• Consequence: HIP1R NM_003959.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0350

Genes affected

HIP1R (HGNC:18415): (huntingtin interacting protein 1 related) Enables several functions, including phosphatidylinositol phosphate binding activity; phosphatidylinositol-3,4-bisphosphate binding activity; and protein homodimerization activity. Involved in several processes, including positive regulation of signal transduction; protein stabilization; and regulation of organelle organization. Located in clathrin-coated vesicle; cytosol; and ruffle membrane. [provided by Alliance of Genome Resources, Apr 2022]

HIP1R (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.511 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HIP1R	NM_003959.3	c.94-5980G>T		intron_variant		ENST00000253083.9	NP_003950.1
HIP1R	NM_001303097.2	c.94-5980G>T		intron_variant			NP_001290026.1
HIP1R	NM_001303099.2	c.58-5980G>T		intron_variant			NP_001290028.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HIP1R	ENST00000253083.9	c.94-5980G>T		intron_variant		1	NM_003959.3	ENSP00000253083.4
HIP1R	ENST00000452196.6	n.164-5980G>T		intron_variant		1
HIP1R	ENST00000535831.5	n.555-5980G>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.286 AC: 43444 AN: 151940 Hom.: 7349 Cov.: 32

Gnomad AFR AF: 0.0961

Gnomad AMI AF: 0.155

Gnomad AMR AF: 0.379

Gnomad ASJ AF: 0.376

Gnomad EAS AF: 0.527

Gnomad SAS AF: 0.421

Gnomad FIN AF: 0.330

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.342

Gnomad OTH AF: 0.313

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.286 AC: 43460 AN: 152058 Hom.: 7355 Cov.: 32 AF XY: 0.292 AC XY: 21710 AN XY: 74340

Gnomad4 AFR AF: 0.0959

Gnomad4 AMR AF: 0.378

Gnomad4 ASJ AF: 0.376

Gnomad4 EAS AF: 0.527

Gnomad4 SAS AF: 0.422

Gnomad4 FIN AF: 0.330

Gnomad4 NFE AF: 0.342

Gnomad4 OTH AF: 0.317

Alfa AF: 0.300 Hom.: 2427

Bravo AF: 0.277

Asia WGS AF: 0.471 AC: 1638 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.1
DANN	Benign	0.77

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: rs10847864; hg19: chr12-123326598;