rs6854783

Variant names:

• chr4-144721927-G-A
• rs6854783
• NM_022475.3:c.1760+2971G>A

Your query was ambiguous. Multiple possible variants found:

• chr4-144721927-G-A
• chr4-144721927-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022475.3(HHIP):​c.1760+2971G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.571 in 149,938 control chromosomes in the GnomAD database, including 24,705 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 0.57 (24705 hom., cov: 29)
• Consequence: HHIP NM_022475.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.710
• Publications: 41 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.736 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HHIP	NM_022475.3	MANE Select	c.1760+2971G>A		intron	N/A	NP_071920.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HHIP	ENST00000296575.8	TSL:1 MANE Select	c.1760+2971G>A		intron	N/A	ENSP00000296575.3
	ENSG00000285713	ENST00000649263.1		n.328-305949C>T		intron	N/A	ENSP00000497507.1
	HHIP	ENST00000911099.1		c.1790+2971G>A		intron	N/A	ENSP00000581158.1

Frequencies

GnomAD3 genomes AF: 0.571 AC: 85498 AN: 149862 Hom.: 24675 Cov.: 29

Gnomad AFR AF: 0.482

Gnomad AMI AF: 0.579

Gnomad AMR AF: 0.648

Gnomad ASJ AF: 0.573

Gnomad EAS AF: 0.498

Gnomad SAS AF: 0.756

Gnomad FIN AF: 0.646

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.589

Gnomad OTH AF: 0.543

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

GnomAD4 genome AF: 0.571 AC: 85566 AN: 149938 Hom.: 24705 Cov.: 29 AF XY: 0.577 AC XY: 42111 AN XY: 73044

African (AFR) AF: 0.482 AC: 19675 AN: 40784

American (AMR) AF: 0.648 AC: 9841 AN: 15176

Ashkenazi Jewish (ASJ) AF: 0.573 AC: 1981 AN: 3460

East Asian (EAS) AF: 0.498 AC: 2547 AN: 5118

South Asian (SAS) AF: 0.757 AC: 3610 AN: 4770

European-Finnish (FIN) AF: 0.646 AC: 6333 AN: 9800

Middle Eastern (MID) AF: 0.538 AC: 156 AN: 290

European-Non Finnish (NFE) AF: 0.589 AC: 39758 AN: 67538

Other (OTH) AF: 0.544 AC: 1139 AN: 2094

Alfa AF: 0.582 Hom.: 113904

Bravo AF: 0.560

Asia WGS AF: 0.585 AC: 1942 AN: 3322

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.52
DANN	Benign	0.69
PhyloP100		-0.71
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: rs6854783; hg19: chr4-145643079;