rs2220514

Variant names:

• chr4-144655406-G-A
• rs2220514
• NM_022475.3:c.472+2609G>A

Your query was ambiguous. Multiple possible variants found:

• chr4-144655406-G-A
• chr4-144655406-G-T

Variant summary

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

The NM_022475.3(HHIP):​c.472+2609G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.368 in 151,950 control chromosomes in the GnomAD database, including 11,466 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 0.37 (11466 hom., cov: 32)
• Consequence: HHIP NM_022475.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.445
• Publications: 4 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:):

HHIP-AS1 (HGNC:44182): (HHIP antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.502 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022475.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HHIP	NM_022475.3	MANE Select	c.472+2609G>A		intron	N/A	NP_071920.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HHIP	ENST00000296575.8	TSL:1 MANE Select	c.472+2609G>A		intron	N/A	ENSP00000296575.3
	HHIP	ENST00000434550.2	TSL:1	c.472+2609G>A		intron	N/A	ENSP00000408587.2
	ENSG00000285713	ENST00000649263.1		n.328-239428C>T		intron	N/A	ENSP00000497507.1

Frequencies

GnomAD3 genomes AF: 0.369 AC: 55957 AN: 151832 Hom.: 11467 Cov.: 32

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.490

Gnomad AMR AF: 0.413

Gnomad ASJ AF: 0.452

Gnomad EAS AF: 0.216

Gnomad SAS AF: 0.520

Gnomad FIN AF: 0.469

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.452

Gnomad OTH AF: 0.373

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

GnomAD4 genome AF: 0.368 AC: 55973 AN: 151950 Hom.: 11466 Cov.: 32 AF XY: 0.372 AC XY: 27638 AN XY: 74248

African (AFR) AF: 0.181 AC: 7506 AN: 41464

American (AMR) AF: 0.414 AC: 6318 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.452 AC: 1569 AN: 3468

East Asian (EAS) AF: 0.216 AC: 1113 AN: 5152

South Asian (SAS) AF: 0.519 AC: 2492 AN: 4802

European-Finnish (FIN) AF: 0.469 AC: 4956 AN: 10560

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.452 AC: 30684 AN: 67934

Other (OTH) AF: 0.368 AC: 775 AN: 2106

Alfa AF: 0.419 Hom.: 6917

Bravo AF: 0.354

Asia WGS AF: 0.319 AC: 1110 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.35
DANN	Benign	0.51
PhyloP100		-0.45
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: rs2220514; hg19: chr4-145576558;