NM_022475.3:c.1760+3218G>C

Variant names:

• chr4-144722174-G-C
• rs6855202
• NM_022475.3:c.1760+3218G>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.1760+3218G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.578 in 151,918 control chromosomes in the GnomAD database, including 25,629 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 0.58 (25629 hom., cov: 31)
• Consequence: HHIP NM_022475.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0860
• Publications: 6 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=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.74 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.1760+3218G>C		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.1760+3218G>C		intron	N/A	ENSP00000296575.3
	ENSG00000285713	ENST00000649263.1		n.328-306196C>G		intron	N/A	ENSP00000497507.1
	HHIP	ENST00000911099.1		c.1790+3218G>C		intron	N/A	ENSP00000581158.1

Frequencies

GnomAD3 genomes AF: 0.578 AC: 87677 AN: 151804 Hom.: 25584 Cov.: 31

Gnomad AFR AF: 0.509

Gnomad AMI AF: 0.578

Gnomad AMR AF: 0.650

Gnomad ASJ AF: 0.573

Gnomad EAS AF: 0.497

Gnomad SAS AF: 0.760

Gnomad FIN AF: 0.637

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.588

Gnomad OTH AF: 0.553

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

GnomAD4 genome AF: 0.578 AC: 87780 AN: 151918 Hom.: 25629 Cov.: 31 AF XY: 0.583 AC XY: 43273 AN XY: 74262

African (AFR) AF: 0.510 AC: 21117 AN: 41422

American (AMR) AF: 0.651 AC: 9931 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.573 AC: 1988 AN: 3470

East Asian (EAS) AF: 0.497 AC: 2556 AN: 5140

South Asian (SAS) AF: 0.760 AC: 3655 AN: 4808

European-Finnish (FIN) AF: 0.637 AC: 6711 AN: 10540

Middle Eastern (MID) AF: 0.541 AC: 158 AN: 292

European-Non Finnish (NFE) AF: 0.588 AC: 39970 AN: 67962

Other (OTH) AF: 0.554 AC: 1168 AN: 2110

Alfa AF: 0.582 Hom.: 3207

Bravo AF: 0.569

Asia WGS AF: 0.611 AC: 2121 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	4.4
DANN	Benign	0.29
PhyloP100		-0.086
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: rs6855202; hg19: chr4-145643326;