rs12944712

Variant names:

• chr17-45793781-G-A
• rs12944712
• NM_004382.5:c.33+9204G>A

Variant summary

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

The NM_004382.5(CRHR1):​c.33+9204G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.351 in 152,116 control chromosomes in the GnomAD database, including 10,268 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 0.35 (10268 hom., cov: 33)
• Consequence: CRHR1 NM_004382.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.157
• Publications: 41 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.45 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRHR1	NM_004382.5	c.33+9204G>A		intron_variant	Intron 1 of 12	ENST00000314537.10	NP_004373.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRHR1	ENST00000314537.10	c.33+9204G>A		intron_variant	Intron 1 of 12	1	NM_004382.5	ENSP00000326060.6
LINC02210-CRHR1	ENST00000634540.1	c.-492-13229G>A		intron_variant	Intron 3 of 14	2		ENSP00000488912.1

Frequencies

GnomAD3 genomes AF: 0.351 AC: 53358 AN: 151998 Hom.: 10262 Cov.: 33

Gnomad AFR AF: 0.231

Gnomad AMI AF: 0.477

Gnomad AMR AF: 0.354

Gnomad ASJ AF: 0.401

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.273

Gnomad FIN AF: 0.280

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.454

Gnomad OTH AF: 0.374

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.351 AC: 53374 AN: 152116 Hom.: 10268 Cov.: 33 AF XY: 0.338 AC XY: 25138 AN XY: 74358

African (AFR) AF: 0.231 AC: 9574 AN: 41486

American (AMR) AF: 0.353 AC: 5395 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.401 AC: 1394 AN: 3472

East Asian (EAS) AF: 0.103 AC: 533 AN: 5176

South Asian (SAS) AF: 0.273 AC: 1318 AN: 4822

European-Finnish (FIN) AF: 0.280 AC: 2965 AN: 10594

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.454 AC: 30846 AN: 67966

Other (OTH) AF: 0.372 AC: 788 AN: 2116

Alfa AF: 0.424 Hom.: 8528

Bravo AF: 0.351

Asia WGS AF: 0.203 AC: 707 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.3
DANN	Benign	0.23
PhyloP100		0.16
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: rs12944712; hg19: chr17-43871147;