NM_001525.3:c.237A>G

Variant names:

• chr1-31619569-A-G
• rs111252644
• NM_001525.3:c.237A>G

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001525.3(HCRTR1):​c.237A>G​(p.Thr79Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00419 in 1,614,126 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0031 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0043 (12 hom.)
• Consequence: HCRTR1 NM_001525.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.57
• Publications: 1 publications found

Genes affected

HCRTR1 (HGNC:4848): (hypocretin receptor 1) The protein encoded by this gene is a G-protein coupled receptor involved in the regulation of feeding behavior. The encoded protein selectively binds the hypothalamic neuropeptide orexin A. A related gene (HCRTR2) encodes a G-protein coupled receptor that binds orexin A and orexin B. [provided by RefSeq, Jan 2009]

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 1-31619569-A-G is Benign according to our data. Variant chr1-31619569-A-G is described in ClinVar as Benign. ClinVar VariationId is 779395.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-4.57 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001525.3. 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
	HCRTR1	NM_001525.3	MANE Select	c.237A>G	p.Thr79Thr	synonymous	Exon 4 of 9	NP_001516.2	O43613

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HCRTR1	ENST00000403528.7	TSL:5 MANE Select	c.237A>G	p.Thr79Thr	synonymous	Exon 4 of 9	ENSP00000384387.2	O43613
	HCRTR1	ENST00000373706.9	TSL:1	c.237A>G	p.Thr79Thr	synonymous	Exon 2 of 7	ENSP00000362810.5	O43613
	HCRTR1	ENST00000373705.1	TSL:1	c.237A>G	p.Thr79Thr	synonymous	Exon 2 of 7	ENSP00000362809.1	A6NMV7

Frequencies

GnomAD3 genomes AF: 0.00308 AC: 469 AN: 152194 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000654

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00527

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00523

Gnomad OTH AF: 0.00335

GnomAD2 exomes AF: 0.00362 AC: 908 AN: 251136 AF XY: 0.00361

Gnomad AFR exome AF: 0.000431

Gnomad AMR exome AF: 0.000434

Gnomad ASJ exome AF: 0.000497

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00653

Gnomad NFE exome AF: 0.00608

Gnomad OTH exome AF: 0.00261

GnomAD4 exome AF: 0.00431 AC: 6302 AN: 1461814 Hom.: 12 Cov.: 33 AF XY: 0.00421 AC XY: 3065 AN XY: 727214

African (AFR) AF: 0.000657 AC: 22 AN: 33480

American (AMR) AF: 0.000582 AC: 26 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.000421 AC: 11 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000893 AC: 77 AN: 86256

European-Finnish (FIN) AF: 0.00639 AC: 341 AN: 53384

Middle Eastern (MID) AF: 0.000694 AC: 4 AN: 5766

European-Non Finnish (NFE) AF: 0.00507 AC: 5639 AN: 1111994

Other (OTH) AF: 0.00301 AC: 182 AN: 60396

GnomAD4 genome AF: 0.00308 AC: 469 AN: 152312 Hom.: 2 Cov.: 33 AF XY: 0.00294 AC XY: 219 AN XY: 74486

African (AFR) AF: 0.000722 AC: 30 AN: 41570

American (AMR) AF: 0.000653 AC: 10 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.000864 AC: 3 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4826

European-Finnish (FIN) AF: 0.00527 AC: 56 AN: 10632

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00523 AC: 356 AN: 68012

Other (OTH) AF: 0.00331 AC: 7 AN: 2112

Alfa AF: 0.00422 Hom.: 1

Bravo AF: 0.00264

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00414

EpiControl AF: 0.00433

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.012
DANN	Benign	0.52
PhyloP100		-4.6
PromoterAI		-0.017	Neutral
Mutation Taster		=100/0	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: rs111252644; hg19: chr1-32085170;