rs17721701

Variant names:

• chr4-144697567-T-C
• rs17721701
• NM_022475.3:c.832-8964T>C

Variant summary

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

The NM_022475.3(HHIP):​c.832-8964T>C 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 151,782 control chromosomes in the GnomAD database, including 20,257 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 (20257 hom., cov: 32)
• Consequence: HHIP NM_022475.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.970
• Publications: 9 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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.749 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HHIP	NM_022475.3	c.832-8964T>C		intron_variant	Intron 4 of 12	ENST00000296575.8	NP_071920.1
LOC124900791	XR_007058289.1	n.8698A>G		non_coding_transcript_exon_variant	Exon 2 of 2
HHIP	XM_005263178.6	c.832-8964T>C		intron_variant	Intron 4 of 13		XP_005263235.1
HHIP	XM_006714288.5	c.832-8964T>C		intron_variant	Intron 4 of 13		XP_006714351.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HHIP	ENST00000296575.8	c.832-8964T>C		intron_variant	Intron 4 of 12	1	NM_022475.3	ENSP00000296575.3
ENSG00000285713	ENST00000649263.1	n.328-281589A>G		intron_variant	Intron 4 of 8			ENSP00000497507.1
ENSG00000285783	ENST00000650526.1	n.222+57590A>G		intron_variant	Intron 2 of 14

Frequencies

GnomAD3 genomes AF: 0.502 AC: 76205 AN: 151664 Hom.: 20229 Cov.: 32

Gnomad AFR AF: 0.322

Gnomad AMI AF: 0.537

Gnomad AMR AF: 0.557

Gnomad ASJ AF: 0.568

Gnomad EAS AF: 0.425

Gnomad SAS AF: 0.769

Gnomad FIN AF: 0.587

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.571

Gnomad OTH AF: 0.487

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

GnomAD4 genome AF: 0.503 AC: 76271 AN: 151782 Hom.: 20257 Cov.: 32 AF XY: 0.507 AC XY: 37571 AN XY: 74164

African (AFR) AF: 0.322 AC: 13341 AN: 41410

American (AMR) AF: 0.558 AC: 8489 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.568 AC: 1965 AN: 3462

East Asian (EAS) AF: 0.425 AC: 2190 AN: 5152

South Asian (SAS) AF: 0.770 AC: 3716 AN: 4826

European-Finnish (FIN) AF: 0.587 AC: 6194 AN: 10552

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.571 AC: 38710 AN: 67846

Other (OTH) AF: 0.488 AC: 1027 AN: 2106

Alfa AF: 0.557 Hom.: 18322

Bravo AF: 0.486

Asia WGS AF: 0.582 AC: 2018 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.54
DANN	Benign	0.58
PhyloP100		-0.97
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: rs17721701; hg19: chr4-145618719;