rs6537310

Variant names:

• chr4-144715580-T-A
• rs6537310
• NM_022475.3:c.1678+150T>A

Your query was ambiguous. Multiple possible variants found:

• chr4-144715580-T-A
• chr4-144715580-T-C
• chr4-144715580-T-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_022475.3(HHIP):​c.1678+150T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000424 in 472,154 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000042 (0 hom.)
• Consequence: HHIP NM_022475.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.117
• Publications: 7 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HHIP	NM_022475.3	c.1678+150T>A		intron_variant	Intron 10 of 12	ENST00000296575.8	NP_071920.1
HHIP	XM_005263178.6	c.1678+150T>A		intron_variant	Intron 10 of 13		XP_005263235.1
HHIP	XM_006714288.5	c.1678+150T>A		intron_variant	Intron 10 of 13		XP_006714351.1
LOC124900791	XR_007058289.1	n.1305-10620A>T		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HHIP	ENST00000296575.8	c.1678+150T>A		intron_variant	Intron 10 of 12	1	NM_022475.3	ENSP00000296575.3
ENSG00000285713	ENST00000649263.1	n.328-299602A>T		intron_variant	Intron 4 of 8			ENSP00000497507.1
HHIP	ENST00000512791.1	n.781T>A		non_coding_transcript_exon_variant	Exon 5 of 5	4
ENSG00000285783	ENST00000650526.1	n.222+39577A>T		intron_variant	Intron 2 of 14

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000424 AC: 2 AN: 472154 Hom.: 0 Cov.: 7 AF XY: 0.00000411 AC XY: 1 AN XY: 243252

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 12852

American (AMR) AF: 0.00 AC: 0 AN: 17050

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11766

East Asian (EAS) AF: 0.00 AC: 0 AN: 28520

South Asian (SAS) AF: 0.00 AC: 0 AN: 28722

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27156

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1782

European-Non Finnish (NFE) AF: 0.00000625 AC: 2 AN: 319756

Other (OTH) AF: 0.00 AC: 0 AN: 24550

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 11837

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.55
DANN	Benign	0.33
PhyloP100		-0.12

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: rs6537310; hg19: chr4-145636732;