rs2306924

Variant names:

• chr4-144661384-A-G
• rs2306924
• NM_022475.3:c.831+1546A>G

Your query was ambiguous. Multiple possible variants found:

• chr4-144661384-A-G
• chr4-144661384-A-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.831+1546A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.563 in 152,020 control chromosomes in the GnomAD database, including 24,487 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 0.56 (24487 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: HHIP NM_022475.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.181
• 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:):

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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.714 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HHIP	NM_022475.3	MANE Select	c.831+1546A>G		intron	N/A	NP_071920.1	Q96QV1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HHIP	ENST00000296575.8	TSL:1 MANE Select	c.831+1546A>G		intron	N/A	ENSP00000296575.3	Q96QV1-1
	ENSG00000285713	ENST00000649263.1		n.328-245406T>C		intron	N/A	ENSP00000497507.1	A0A3B3ISY7
	HHIP	ENST00000911099.1		c.831+1546A>G		intron	N/A	ENSP00000581158.1

Frequencies

GnomAD3 genomes AF: 0.563 AC: 85516 AN: 151902 Hom.: 24432 Cov.: 32

Gnomad AFR AF: 0.659

Gnomad AMI AF: 0.544

Gnomad AMR AF: 0.557

Gnomad ASJ AF: 0.542

Gnomad EAS AF: 0.424

Gnomad SAS AF: 0.733

Gnomad FIN AF: 0.542

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.510

Gnomad OTH AF: 0.525

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.563 AC: 85638 AN: 152020 Hom.: 24487 Cov.: 32 AF XY: 0.565 AC XY: 41985 AN XY: 74300

African (AFR) AF: 0.660 AC: 27325 AN: 41422

American (AMR) AF: 0.558 AC: 8526 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.542 AC: 1882 AN: 3472

East Asian (EAS) AF: 0.425 AC: 2201 AN: 5184

South Asian (SAS) AF: 0.734 AC: 3539 AN: 4822

European-Finnish (FIN) AF: 0.542 AC: 5721 AN: 10548

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.510 AC: 34694 AN: 67974

Other (OTH) AF: 0.526 AC: 1110 AN: 2112

Alfa AF: 0.534 Hom.: 57215

Bravo AF: 0.561

Asia WGS AF: 0.579 AC: 2013 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.5
DANN	Benign	0.49
PhyloP100		-0.18
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2306924; hg19: chr4-145582536;