rs1492820

Variant names:

• chr4-144728869-G-A
• rs1492820
• NM_022475.3:c.1761-5872G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022475.3(HHIP):​c.1761-5872G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.503 in 151,880 control chromosomes in the GnomAD database, including 20,189 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 0.50 (20189 hom., cov: 31)
• Consequence: HHIP NM_022475.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.562
• Publications: 30 publications found

Genes affected

HHIP (HGNC:14866): (hedgehog interacting protein) This gene encodes a member of the hedgehog-interacting protein (HHIP) family. The hedgehog (HH) proteins are evolutionarily conserved protein, which are important morphogens for a wide range of developmental processes, including anteroposterior patterns of limbs and regulation of left-right asymmetry in embryonic development. Multiple cell-surface receptors are responsible for transducing and/or regulating HH signals. The HHIP encoded by this gene is a highly conserved, vertebrate-specific inhibitor of HH signaling. It interacts with all three HH family members, SHH, IHH and DHH. Two single nucleotide polymorphisms (SNPs) near this gene are significantly associated with risk of chronic obstructive pulmonary disease (COPD). A single nucleotide polymorphism in this gene is also strongly associated with human height.[provided by RefSeq, Feb 2011]

ENSG00000285713 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.7 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HHIP	NM_022475.3	c.1761-5872G>A		intron_variant	Intron 11 of 12	ENST00000296575.8	NP_071920.1
HHIP	XM_005263178.6	c.1761-5872G>A		intron_variant	Intron 11 of 13		XP_005263235.1
HHIP	XM_006714288.5	c.1761-5872G>A		intron_variant	Intron 11 of 13		XP_006714351.1
LOC124900791	XR_007058289.1	n.1305-23909C>T		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HHIP	ENST00000296575.8	c.1761-5872G>A		intron_variant	Intron 11 of 12	1	NM_022475.3	ENSP00000296575.3
ENSG00000285713	ENST00000649263.1	n.328-312891C>T		intron_variant	Intron 4 of 8			ENSP00000497507.1
ENSG00000285783	ENST00000650526.1	n.222+26288C>T		intron_variant	Intron 2 of 14

Frequencies

GnomAD3 genomes AF: 0.503 AC: 76334 AN: 151762 Hom.: 20168 Cov.: 31

Gnomad AFR AF: 0.338

Gnomad AMI AF: 0.546

Gnomad AMR AF: 0.611

Gnomad ASJ AF: 0.505

Gnomad EAS AF: 0.495

Gnomad SAS AF: 0.721

Gnomad FIN AF: 0.607

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.548

Gnomad OTH AF: 0.479

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

GnomAD4 genome AF: 0.503 AC: 76384 AN: 151880 Hom.: 20189 Cov.: 31 AF XY: 0.512 AC XY: 37977 AN XY: 74220

African (AFR) AF: 0.338 AC: 14006 AN: 41400

American (AMR) AF: 0.611 AC: 9320 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.505 AC: 1750 AN: 3462

East Asian (EAS) AF: 0.495 AC: 2557 AN: 5170

South Asian (SAS) AF: 0.720 AC: 3475 AN: 4828

European-Finnish (FIN) AF: 0.607 AC: 6384 AN: 10516

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.548 AC: 37241 AN: 67948

Other (OTH) AF: 0.481 AC: 1014 AN: 2110

Alfa AF: 0.533 Hom.: 97177

Bravo AF: 0.491

Asia WGS AF: 0.577 AC: 2003 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	4.1
DANN	Benign	0.66
PhyloP100		0.56
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1492820; hg19: chr4-145650021;