Variant 4-144714358-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The ENST00000296575.8(HHIP):c.1547+10C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00245 in 1,612,896 control chromosomes in the GnomAD database, including 93 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.013 ( 54 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 39 hom. )

Consequence

HHIP
ENST00000296575.8 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.191

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:

LOC124900791 (HGNC:):

LOC124900791 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 4-144714358-C-G is Benign according to our data. Variant chr4-144714358-C-G is described in ClinVar as [Benign]. Clinvar id is 767979.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0133 (2020/152158) while in subpopulation AFR AF= 0.0464 (1926/41490). AF 95% confidence interval is 0.0447. There are 54 homozygotes in gnomad4. There are 910 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2020 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
HHIP	NM_022475.3 linkuse as main transcript	c.1547+10C>G	intron_variant	ENST00000296575.8	NP_071920.1
LOC124900791	XR_007058289.1 linkuse as main transcript	n.1305-9398G>C	intron_variant, non_coding_transcript_variant
HHIP	XM_005263178.6 linkuse as main transcript	c.1547+10C>G	intron_variant		XP_005263235.1
HHIP	XM_006714288.5 linkuse as main transcript	c.1547+10C>G	intron_variant		XP_006714351.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HHIP	ENST00000296575.8 linkuse as main transcript	c.1547+10C>G		intron_variant		1	NM_022475.3	ENSP00000296575	P1	Q96QV1-1
HHIP	ENST00000512791.1 linkuse as main transcript	n.427+10C>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes

AF:

0.0132

AC:

2011

AN:

152040

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0463

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00348

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000294

Gnomad OTH

AF:

0.00956

GnomAD3 exomes

AF:

0.00335

AC:

839

AN:

250500

Hom.:

AF XY:

0.00238

AC XY:

322

AN XY:

135392

show subpopulations

Gnomad AFR exome

AF:

0.0471

Gnomad AMR exome

AF:

0.00148

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000262

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000619

Gnomad OTH exome

AF:

0.00131

GnomAD4 exome

AF:

0.00132

AC:

1934

AN:

1460738

Hom.:

Cov.:

AF XY:

0.00113

AC XY:

820

AN XY:

726676

show subpopulations

Gnomad4 AFR exome

AF:

0.0473

Gnomad4 AMR exome

AF:

0.00190

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000186

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000513

Gnomad4 OTH exome

AF:

0.00303

GnomAD4 genome

AF:

0.0133

AC:

2020

AN:

152158

Hom.:

Cov.:

AF XY:

0.0122

AC XY:

910

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.0464

Gnomad4 AMR

AF:

0.00347

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000294

Gnomad4 OTH

AF:

0.00946

Alfa

AF:

0.00643

Hom.:

Bravo

AF:

0.0147

Asia WGS

AF:

0.00404

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

6.7

DANN

Benign

0.37

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over