rs61730970

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_022475.3(HHIP):c.707G>A(p.Gly236Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00392 in 1,609,180 control chromosomes in the GnomAD database, including 216 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.021 ( 114 hom., cov: 33)

Exomes 𝑓: 0.0022 ( 102 hom. )

Consequence

HHIP
NM_022475.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 8.15

Publications

9 publications found

Variant links:

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]

HHIP links:

ENSG00000285713 (HGNC:):

ENSG00000285713 links:

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

HHIP-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008589804).

BP6

Variant 4-144659714-G-A is Benign according to our data. Variant chr4-144659714-G-A is described in ClinVar as Benign. ClinVar VariationId is 767978.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0689 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.707G>A	p.Gly236Glu	missense	Exon 4 of 13	NP_071920.1	Q96QV1-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HHIP	ENST00000296575.8	TSL:1 MANE Select	c.707G>A	p.Gly236Glu	missense	Exon 4 of 13	ENSP00000296575.3	Q96QV1-1
HHIP	ENST00000434550.2	TSL:1	c.707G>A	p.Gly236Glu	missense	Exon 4 of 4	ENSP00000408587.2	Q96QV1-2
ENSG00000285713	ENST00000649263.1		n.328-243736C>T		intron	N/A	ENSP00000497507.1	A0A3B3ISY7

Frequencies

GnomAD3 genomes

AF:

0.0205

AC:

3124

AN:

152100

Hom.:

114

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0709

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00844

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.000309

Gnomad OTH

AF:

0.0163

GnomAD2 exomes

AF:

0.00537

AC:

1327

AN:

247294

AF XY:

0.00370

show subpopulations

Gnomad AFR exome

AF:

0.0720

Gnomad AMR exome

AF:

0.00330

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000240

Gnomad OTH exome

AF:

0.00300

GnomAD4 exome

AF:

0.00218

AC:

3174

AN:

1456962

Hom.:

102

Cov.:

AF XY:

0.00185

AC XY:

1343

AN XY:

724574

show subpopulations

African (AFR)

AF:

0.0738

AC:

2446

AN:

33152

American (AMR)

AF:

0.00431

AC:

189

AN:

43814

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25908

East Asian (EAS)

AF:

0.00

AC:

AN:

39618

South Asian (SAS)

AF:

0.000318

AC:

AN:

85004

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53274

Middle Eastern (MID)

AF:

0.00209

AC:

AN:

5732

European-Non Finnish (NFE)

AF:

0.000159

AC:

177

AN:

1110280

Other (OTH)

AF:

0.00537

AC:

323

AN:

60180

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

149

298

446

595

744

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

176

264

352

440

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0206

AC:

3140

AN:

152218

Hom.:

114

Cov.:

AF XY:

0.0196

AC XY:

1460

AN XY:

74414

show subpopulations

African (AFR)

AF:

0.0711

AC:

2950

AN:

41506

American (AMR)

AF:

0.00843

AC:

129

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000309

AC:

AN:

68026

Other (OTH)

AF:

0.0161

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

153

305

458

610

763

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

160

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00687

Hom.:

103

Bravo

AF:

0.0236

ESP6500AA

AF:

0.0731

AC:

322

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.00681

AC:

827

Asia WGS

AF:

0.00520

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.30

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.33

Eigen

Pathogenic

0.71

Eigen_PC

Pathogenic

0.72

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.95

MetaRNN

Benign

0.0086

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.1

PhyloP100

8.1

PrimateAI

Uncertain

0.64

PROVEAN

Uncertain

-4.1

REVEL

Uncertain

0.33

Sift

Uncertain

0.026

Sift4G

Uncertain

0.010

Polyphen

1.0

Vest4

0.71

MVP

0.38

MPC

0.90

ClinPred

0.022

GERP RS

4.7

Varity_R

0.90

gMVP

0.80

Mutation Taster

=34/66

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over