chr17-45835420-G-C

Variant names:

• chr17-45835420-G-C
• rs4640231
• NM_004382.5:c.*656G>C

Variant summary

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

The NM_004382.5(CRHR1):​c.*656G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 153,568 control chromosomes in the GnomAD database, including 2,166 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 0.14 (2142 hom., cov: 33)
  • Exomes 𝑓: 0.16 (24 hom.)
• Consequence: CRHR1 NM_004382.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.548
• Publications: 42 publications found

Genes affected

CRHR1 (HGNC:2357): (corticotropin releasing hormone receptor 1) This gene encodes a G-protein coupled receptor that binds neuropeptides of the corticotropin releasing hormone family that are major regulators of the hypothalamic-pituitary-adrenal pathway. The encoded protein is essential for the activation of signal transduction pathways that regulate diverse physiological processes including stress, reproduction, immune response and obesity. Alternative splicing results in multiple transcript variants. Naturally-occurring readthrough transcription between this gene and upstream GeneID:147081 results in transcripts that encode isoforms that share similarity with the products of this gene. [provided by RefSeq, Aug 2016]

LINC02210-CRHR1 (HGNC:51483): (LINC02210-CRHR1 readthrough) This locus represents naturally occurring readthrough transcription between neighboring genes CRHR1-IT1, CRHR1 intronic transcript 1 (Gene ID: 147081) and CRHR1, corticotropin releasing hormone receptor 1 (Gene ID: 1394) on chromosome 17. The readthrough transcript encodes a protein that shares sequence identity with the product of the CRHR1 gene. [provided by RefSeq, Dec 2016]

MAPT-AS1 (HGNC:43738): (MAPT antisense RNA 1) Implicated in Parkinson's disease. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004382.5. 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
	CRHR1	NM_004382.5	MANE Select	c.*656G>C		3_prime_UTR	Exon 13 of 13	NP_004373.2
	CRHR1	NM_001145146.2		c.*656G>C		3_prime_UTR	Exon 14 of 14	NP_001138618.1	P34998-1
	CRHR1	NM_001145148.2		c.*656G>C		3_prime_UTR	Exon 12 of 12	NP_001138620.1	P34998-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRHR1	ENST00000314537.10	TSL:1 MANE Select	c.*656G>C		3_prime_UTR	Exon 13 of 13	ENSP00000326060.6	P34998-2
	CRHR1	ENST00000398285.7	TSL:1	c.*656G>C		3_prime_UTR	Exon 14 of 14	ENSP00000381333.3	P34998-1
	LINC02210-CRHR1	ENST00000634540.1	TSL:2	c.*656G>C		3_prime_UTR	Exon 15 of 15	ENSP00000488912.1

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21844 AN: 152164 Hom.: 2144 Cov.: 33

Gnomad AFR AF: 0.0430

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0742

Gnomad FIN AF: 0.0652

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.186

GnomAD4 exome AF: 0.164 AC: 211 AN: 1286 Hom.: 24 Cov.: 0 AF XY: 0.175 AC XY: 156 AN XY: 892

African (AFR) AF: 0.125 AC: 2 AN: 16

American (AMR) AF: 0.158 AC: 6 AN: 38

Ashkenazi Jewish (ASJ) AF: 0.375 AC: 3 AN: 8

East Asian (EAS) AF: 0.00 AC: 0 AN: 18

South Asian (SAS) AF: 0.0278 AC: 1 AN: 36

European-Finnish (FIN) AF: 0.0795 AC: 28 AN: 352

Middle Eastern (MID) AF: 0.250 AC: 1 AN: 4

European-Non Finnish (NFE) AF: 0.215 AC: 163 AN: 758

Other (OTH) AF: 0.125 AC: 7 AN: 56

GnomAD4 genome AF: 0.143 AC: 21834 AN: 152282 Hom.: 2142 Cov.: 33 AF XY: 0.134 AC XY: 10001 AN XY: 74474

African (AFR) AF: 0.0429 AC: 1782 AN: 41570

American (AMR) AF: 0.176 AC: 2693 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.241 AC: 836 AN: 3472

East Asian (EAS) AF: 0.00154 AC: 8 AN: 5190

South Asian (SAS) AF: 0.0743 AC: 359 AN: 4834

European-Finnish (FIN) AF: 0.0652 AC: 692 AN: 10612

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.217 AC: 14760 AN: 67982

Other (OTH) AF: 0.183 AC: 387 AN: 2116

Alfa AF: 0.0898 Hom.: 127

Bravo AF: 0.148

Asia WGS AF: 0.0310 AC: 110 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	12
DANN	Benign	0.27
PhyloP100		0.55
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: rs4640231; hg19: chr17-43912786;