17-45821002-A-G

Position:

• chr17-45821002-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000314537.10(CRHR1):​c.242-353A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.56 in 151,716 control chromosomes in the GnomAD database, including 24,613 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 0.56 (24613 hom., cov: 34)
• Consequence: CRHR1 ENST00000314537.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.40

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:):

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

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.845 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRHR1	NM_004382.5	c.242-353A>G		intron_variant		ENST00000314537.10	NP_004373.2
LINC02210-CRHR1	NM_001256299.3	c.-284-353A>G		intron_variant			NP_001243228.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRHR1	ENST00000314537.10	c.242-353A>G		intron_variant		1	NM_004382.5	ENSP00000326060	P1
MAPT-AS1	ENST00000634876.2	n.2593+4581T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.560 AC: 84858 AN: 151600 Hom.: 24606 Cov.: 34

Gnomad AFR AF: 0.434

Gnomad AMI AF: 0.597

Gnomad AMR AF: 0.616

Gnomad ASJ AF: 0.537

Gnomad EAS AF: 0.867

Gnomad SAS AF: 0.780

Gnomad FIN AF: 0.705

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.563

Gnomad OTH AF: 0.543

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

GnomAD4 genome AF: 0.560 AC: 84886 AN: 151716 Hom.: 24613 Cov.: 34 AF XY: 0.572 AC XY: 42413 AN XY: 74182

Gnomad4 AFR AF: 0.433

Gnomad4 AMR AF: 0.617

Gnomad4 ASJ AF: 0.537

Gnomad4 EAS AF: 0.866

Gnomad4 SAS AF: 0.781

Gnomad4 FIN AF: 0.705

Gnomad4 NFE AF: 0.563

Gnomad4 OTH AF: 0.545

Alfa AF: 0.553 Hom.: 4596

Bravo AF: 0.544

Asia WGS AF: 0.780 AC: 2712 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.1
DANN	Benign	0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs242937; hg19: chr17-43898368; COSMIC: COSV53283902; COSMIC: COSV53283902;