Genetic Variant NM_022475.3:c.1678+150T>G (chr4-144715580-T-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_022475.3(HHIP):c.1678+150T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000641 in 624,144 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000042 ( 0 hom. )

Consequence

HHIP
NM_022475.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.117

Publications

7 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
HHIP	NM_022475.3 link	c.1678+150T>G	intron_variant	Intron 10 of 12	ENST00000296575.8	NP_071920.1	Q96QV1-1
HHIP	XM_005263178.6 link	c.1678+150T>G	intron_variant	Intron 10 of 13		XP_005263235.1
HHIP	XM_006714288.5 link	c.1678+150T>G	intron_variant	Intron 10 of 13		XP_006714351.1
LOC124900791	XR_007058289.1 link	n.1305-10620A>C	intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
HHIP	ENST00000296575.8 link	c.1678+150T>G	intron_variant	Intron 10 of 12	1	NM_022475.3	ENSP00000296575.3	Q96QV1-1
ENSG00000285713	ENST00000649263.1 link	n.328-299602A>C	intron_variant	Intron 4 of 8			ENSP00000497507.1	A0A3B3ISY7
HHIP	ENST00000512791.1 link	n.781T>G	non_coding_transcript_exon_variant	Exon 5 of 5	4
ENSG00000285783	ENST00000650526.1 link	n.222+39577A>C	intron_variant	Intron 2 of 14

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151990

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000424

AC:

AN:

472154

Hom.:

Cov.:

AF XY:

0.00000411

AC XY:

AN XY:

243252

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

12852

American (AMR)

AF:

0.000117

AC:

AN:

17050

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

11766

East Asian (EAS)

AF:

0.00

AC:

AN:

28520

South Asian (SAS)

AF:

0.00

AC:

AN:

28722

European-Finnish (FIN)

AF:

0.00

AC:

AN:

27156

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1782

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

319756

Other (OTH)

AF:

0.00

AC:

AN:

24550

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000132

AC:

AN:

151990

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74218

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41370

American (AMR)

AF:

0.000131

AC:

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10574

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67992

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

11837

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.58

(source)

DANN

Benign

0.49

PhyloP100

-0.12

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over