4-144722174-G-C

Position:

• chr4-144722174-G-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HHIP	NM_022475.3	c.1760+3218G>C		intron_variant		ENST00000296575.8	NP_071920.1
HHIP	XM_005263178.6	c.1760+3218G>C		intron_variant			XP_005263235.1
HHIP	XM_006714288.5	c.1760+3218G>C		intron_variant			XP_006714351.1
LOC124900791	XR_007058289.1	n.1305-17214C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HHIP	ENST00000296575.8	c.1760+3218G>C		intron_variant		1	NM_022475.3	ENSP00000296575.3
ENSG00000285713	ENST00000649263.1	n.328-306196C>G		intron_variant				ENSP00000497507.1
ENSG00000285783	ENST00000650526.1	n.222+32983C>G		intron_variant

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

Gnomad4 AFR AF: 0.510

Gnomad4 AMR AF: 0.651

Gnomad4 ASJ AF: 0.573

Gnomad4 EAS AF: 0.497

Gnomad4 SAS AF: 0.760

Gnomad4 FIN AF: 0.637

Gnomad4 NFE AF: 0.588

Gnomad4 OTH AF: 0.554

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	4.4
DANN	Benign	0.29

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

Publications

LitVar

Other links and lift over

dbSNP: rs6855202; hg19: chr4-145643326;