rs6854783

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

LOC124900791 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HHIP	NM_022475.3	c.1760+2971G>A		intron_variant		ENST00000296575.8	NP_071920.1
LOC124900791	XR_007058289.1	n.1305-16967C>T		intron_variant, non_coding_transcript_variant
HHIP	XM_005263178.6	c.1760+2971G>A		intron_variant			XP_005263235.1
HHIP	XM_006714288.5	c.1760+2971G>A		intron_variant			XP_006714351.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HHIP	ENST00000296575.8	c.1760+2971G>A		intron_variant		1	NM_022475.3	ENSP00000296575	P1

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

Gnomad4 AFR AF: 0.482

Gnomad4 AMR AF: 0.648

Gnomad4 ASJ AF: 0.573

Gnomad4 EAS AF: 0.498

Gnomad4 SAS AF: 0.757

Gnomad4 FIN AF: 0.646

Gnomad4 NFE AF: 0.589

Gnomad4 OTH AF: 0.544

Alfa AF: 0.584 Hom.: 56383

Bravo AF: 0.560

Asia WGS AF: 0.585 AC: 1942 AN: 3322

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.52
DANN	Benign	0.69

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: rs6854783; hg19: chr4-145643079;