rs16940646

Positions:

• chr17-45802545-A-C

Variant summary

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

The NM_004382.5(CRHR1):​c.34-4465A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 152,212 control chromosomes in the GnomAD database, including 2,324 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 0.15 (2324 hom., cov: 33)
• Consequence: CRHR1 NM_004382.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.147

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRHR1	NM_004382.5	c.34-4465A>C		intron_variant		ENST00000314537.10
LINC02210-CRHR1	NM_001256299.3	c.-492-4465A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRHR1	ENST00000314537.10	c.34-4465A>C		intron_variant		1	NM_004382.5	P1
MAPT-AS1	ENST00000634876.2	n.2594-1755T>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.145 AC: 22020 AN: 152094 Hom.: 2311 Cov.: 33

Gnomad AFR AF: 0.296

Gnomad AMI AF: 0.0462

Gnomad AMR AF: 0.0846

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0290

Gnomad FIN AF: 0.0902

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0964

Gnomad OTH AF: 0.143

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

GnomAD4 genome AF: 0.145 AC: 22076 AN: 152212 Hom.: 2324 Cov.: 33 AF XY: 0.142 AC XY: 10574 AN XY: 74424

Gnomad4 AFR AF: 0.297

Gnomad4 AMR AF: 0.0846

Gnomad4 ASJ AF: 0.123

Gnomad4 EAS AF: 0.000771

Gnomad4 SAS AF: 0.0290

Gnomad4 FIN AF: 0.0902

Gnomad4 NFE AF: 0.0964

Gnomad4 OTH AF: 0.141

Alfa AF: 0.120 Hom.: 234

Bravo AF: 0.151

Asia WGS AF: 0.0350 AC: 121 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	7.1
DANN	Benign	0.75

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

Publications

LitVar

Other links and lift over

dbSNP: rs16940646; hg19: chr17-43879911;