chr6-55255177-C-T

Variant names:

• chr6-55255177-C-T
• rs113561951
• NM_001384272.1:c.444C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Moderate BP6 BP7 BS2

The NM_001384272.1(HCRTR2):​c.444C>T​(p.Ile148Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00054 in 1,613,896 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0027 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00032 (5 hom.)
• Consequence: HCRTR2 NM_001384272.1 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.103
• Publications: 1 publications found

Genes affected

HCRTR2 (HGNC:4849): (hypocretin receptor 2) The protein encoded by this gene is a G-protein coupled receptor involved in the regulation of feeding behavior. The encoded protein binds the hypothalamic neuropeptides orexin A and orexin B. A related gene (HCRTR1) encodes a G-protein coupled receptor that selectively binds orexin A. [provided by RefSeq, Jan 2009]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BP6: Variant 6-55255177-C-T is Benign according to our data. Variant chr6-55255177-C-T is described in ClinVar as Benign. ClinVar VariationId is 3037159.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-0.103 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001384272.1. 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
	HCRTR2	NM_001384272.1	MANE Select	c.444C>T	p.Ile148Ile	synonymous	Exon 3 of 7	NP_001371201.1	S4X0W3
	HCRTR2	NM_001526.5		c.444C>T	p.Ile148Ile	synonymous	Exon 4 of 8	NP_001517.2	O43614

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HCRTR2	ENST00000370862.4	TSL:1 MANE Select	c.444C>T	p.Ile148Ile	synonymous	Exon 3 of 7	ENSP00000359899.3	O43614
	HCRTR2	ENST00000615358.4	TSL:1	c.444C>T	p.Ile148Ile	synonymous	Exon 4 of 8	ENSP00000477548.1	O43614

Frequencies

GnomAD3 genomes AF: 0.00254 AC: 387 AN: 152064 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00882

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00112

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.000804 AC: 202 AN: 251126 AF XY: 0.000545

Gnomad AFR exome AF: 0.0106

Gnomad AMR exome AF: 0.000723

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000881

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000320 AC: 468 AN: 1461714 Hom.: 5 Cov.: 31 AF XY: 0.000296 AC XY: 215 AN XY: 727162

African (AFR) AF: 0.0101 AC: 338 AN: 33466

American (AMR) AF: 0.000760 AC: 34 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.0000927 AC: 8 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00104 AC: 6 AN: 5766

European-Non Finnish (NFE) AF: 0.0000117 AC: 13 AN: 1111886

Other (OTH) AF: 0.00114 AC: 69 AN: 60388

GnomAD4 genome AF: 0.00265 AC: 404 AN: 152182 Hom.: 2 Cov.: 32 AF XY: 0.00273 AC XY: 203 AN XY: 74390

African (AFR) AF: 0.00920 AC: 382 AN: 41526

American (AMR) AF: 0.00111 AC: 17 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68016

Other (OTH) AF: 0.00142 AC: 3 AN: 2114

Alfa AF: 0.00148 Hom.: 1

Bravo AF: 0.00327

Asia WGS AF: 0.00346 AC: 12 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	HCRTR2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	5.3
DANN	Benign	0.86
PhyloP100		-0.10
Mutation Taster		=98/2	polymorphism

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: rs113561951; hg19: chr6-55119975;