chr4-144666964-A-T

Position:

• chr4-144666964-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022475.3(HHIP):​c.831+7126A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.362 in 152,086 control chromosomes in the GnomAD database, including 11,325 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 0.36 (11325 hom., cov: 32)
• Consequence: HHIP NM_022475.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0570

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.506 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HHIP	NM_022475.3	c.831+7126A>T		intron_variant		ENST00000296575.8
HHIP	XM_005263178.6	c.831+7126A>T		intron_variant
HHIP	XM_006714288.5	c.831+7126A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HHIP	ENST00000296575.8	c.831+7126A>T		intron_variant		1	NM_022475.3	P1
HHIP	ENST00000509630.1	n.498+7126A>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.362 AC: 55004 AN: 151968 Hom.: 11327 Cov.: 32

Gnomad AFR AF: 0.155

Gnomad AMI AF: 0.516

Gnomad AMR AF: 0.411

Gnomad ASJ AF: 0.455

Gnomad EAS AF: 0.214

Gnomad SAS AF: 0.524

Gnomad FIN AF: 0.475

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.452

Gnomad OTH AF: 0.369

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.362 AC: 55020 AN: 152086 Hom.: 11325 Cov.: 32 AF XY: 0.367 AC XY: 27252 AN XY: 74342

Gnomad4 AFR AF: 0.155

Gnomad4 AMR AF: 0.411

Gnomad4 ASJ AF: 0.455

Gnomad4 EAS AF: 0.215

Gnomad4 SAS AF: 0.523

Gnomad4 FIN AF: 0.475

Gnomad4 NFE AF: 0.452

Gnomad4 OTH AF: 0.364

Alfa AF: 0.409 Hom.: 1665

Bravo AF: 0.346

Asia WGS AF: 0.318 AC: 1105 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.3
DANN	Benign	0.48

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: rs6537302; hg19: chr4-145588116;