NM_022475.3:c.831+16769A>G

Variant names:

• chr4-144676607-A-G
• rs2055059
• NM_022475.3:c.831+16769A>G

Variant summary

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

The NM_022475.3(HHIP):​c.831+16769A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.607 in 152,036 control chromosomes in the GnomAD database, including 28,180 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 0.61 (28180 hom., cov: 32)
• Consequence: HHIP NM_022475.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.751
• Publications: 11 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.747 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.831+16769A>G		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.831+16769A>G		intron	N/A	ENSP00000296575.3
	ENSG00000285713	ENST00000649263.1		n.328-260629T>C		intron	N/A	ENSP00000497507.1
	HHIP	ENST00000509630.1	TSL:4	n.499-8994A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.607 AC: 92246 AN: 151918 Hom.: 28128 Cov.: 32

Gnomad AFR AF: 0.646

Gnomad AMI AF: 0.632

Gnomad AMR AF: 0.593

Gnomad ASJ AF: 0.569

Gnomad EAS AF: 0.427

Gnomad SAS AF: 0.767

Gnomad FIN AF: 0.600

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.594

Gnomad OTH AF: 0.566

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

GnomAD4 genome AF: 0.607 AC: 92357 AN: 152036 Hom.: 28180 Cov.: 32 AF XY: 0.608 AC XY: 45165 AN XY: 74322

African (AFR) AF: 0.646 AC: 26779 AN: 41448

American (AMR) AF: 0.594 AC: 9071 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.569 AC: 1974 AN: 3472

East Asian (EAS) AF: 0.427 AC: 2203 AN: 5158

South Asian (SAS) AF: 0.768 AC: 3697 AN: 4816

European-Finnish (FIN) AF: 0.600 AC: 6330 AN: 10558

Middle Eastern (MID) AF: 0.517 AC: 152 AN: 294

European-Non Finnish (NFE) AF: 0.594 AC: 40383 AN: 67990

Other (OTH) AF: 0.565 AC: 1193 AN: 2110

Alfa AF: 0.605 Hom.: 11861

Bravo AF: 0.601

Asia WGS AF: 0.598 AC: 2078 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.73
DANN	Benign	0.67
PhyloP100		-0.75
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: rs2055059; hg19: chr4-145597759;