4-144680711-A-G

Variant names:

• chr4-144680711-A-G
• rs6537307
• NM_022475.3:c.831+20873A>G

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+20873A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.394 in 152,048 control chromosomes in the GnomAD database, including 13,512 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 0.39 (13512 hom., cov: 32)
• Consequence: HHIP NM_022475.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0650
• Publications: 18 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:):

ACMG classification

Our verdict: Benign. The variant received -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 = 0.504 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+20873A>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+20873A>G		intron	N/A	ENSP00000296575.3	Q96QV1-1
	ENSG00000285713	ENST00000649263.1		n.328-264733T>C		intron	N/A	ENSP00000497507.1	A0A3B3ISY7
	HHIP	ENST00000911099.1		c.831+20873A>G		intron	N/A	ENSP00000581158.1

Frequencies

GnomAD3 genomes AF: 0.394 AC: 59875 AN: 151930 Hom.: 13518 Cov.: 32

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.480

Gnomad AMR AF: 0.427

Gnomad ASJ AF: 0.457

Gnomad EAS AF: 0.182

Gnomad SAS AF: 0.523

Gnomad FIN AF: 0.525

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.505

Gnomad OTH AF: 0.395

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

GnomAD4 genome AF: 0.394 AC: 59878 AN: 152048 Hom.: 13512 Cov.: 32 AF XY: 0.397 AC XY: 29528 AN XY: 74330

African (AFR) AF: 0.170 AC: 7055 AN: 41508

American (AMR) AF: 0.427 AC: 6513 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.457 AC: 1583 AN: 3462

East Asian (EAS) AF: 0.183 AC: 947 AN: 5180

South Asian (SAS) AF: 0.521 AC: 2515 AN: 4824

European-Finnish (FIN) AF: 0.525 AC: 5544 AN: 10558

Middle Eastern (MID) AF: 0.449 AC: 131 AN: 292

European-Non Finnish (NFE) AF: 0.505 AC: 34329 AN: 67944

Other (OTH) AF: 0.390 AC: 823 AN: 2112

Alfa AF: 0.478 Hom.: 13802

Bravo AF: 0.374

Asia WGS AF: 0.308 AC: 1070 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.5
DANN	Benign	0.41
PhyloP100		-0.065
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6537307; hg19: chr4-145601863;