7-75606231-T-G

Variant summary

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

The NM_005338.7(HIP1):c.121-6984A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 152,124 control chromosomes in the GnomAD database, including 2,319 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 0.14 (2319 hom., cov: 31)
• Consequence: HIP1 NM_005338.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.230

Genes affected

HIP1 (HGNC:4913): (huntingtin interacting protein 1) The product of this gene is a membrane-associated protein that functions in clathrin-mediated endocytosis and protein trafficking within the cell. The encoded protein binds to the huntingtin protein in the brain; this interaction is lost in Huntington's disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.259 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HIP1	NM_005338.7	c.121-6984A>C		intron_variant		ENST00000336926.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HIP1	ENST00000336926.11	c.121-6984A>C		intron_variant		1	NM_005338.7	P1
HIP1	ENST00000616821.4	c.33+5435A>C		intron_variant		1
HIP1	ENST00000420909.1	c.33+5435A>C		intron_variant		3
HIP1	ENST00000434438.6	c.121-6984A>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.136 AC: 20737 AN: 152006 Hom.: 2309 Cov.: 31

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.0608

Gnomad EAS AF: 0.251

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.0659

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0451

Gnomad OTH AF: 0.134

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

GnomAD4 genome AF: 0.137 AC: 20777 AN: 152124 Hom.: 2319 Cov.: 31 AF XY: 0.140 AC XY: 10380 AN XY: 74384

Gnomad4 AFR AF: 0.263

Gnomad4 AMR AF: 0.217

Gnomad4 ASJ AF: 0.0608

Gnomad4 EAS AF: 0.251

Gnomad4 SAS AF: 0.199

Gnomad4 FIN AF: 0.0659

Gnomad4 NFE AF: 0.0451

Gnomad4 OTH AF: 0.134

Alfa AF: 0.0633 Hom.: 537

Bravo AF: 0.153

Asia WGS AF: 0.229 AC: 794 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	1.9
Dann	Benign	0.47

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: rs17149227; hg19: chr7-75235549;