rs28364028

Positions:

• chr17-45816745-T-A
• chr17-45816745-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_004382.5(CRHR1):​c.241+163T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0102 in 152,342 control chromosomes in the GnomAD database, including 18 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 0.010 (18 hom., cov: 33)
• Consequence: CRHR1 NM_004382.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.16

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=-0.79).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0102 (1559/152342) while in subpopulation NFE AF= 0.016 (1091/68014). AF 95% confidence interval is 0.0152. There are 18 homozygotes in gnomad4. There are 722 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1559 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRHR1	NM_004382.5	c.241+163T>A		intron_variant		ENST00000314537.10
LINC02210-CRHR1	NM_001256299.3	c.-285+163T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRHR1	ENST00000314537.10	c.241+163T>A		intron_variant		1	NM_004382.5	P1
MAPT-AS1	ENST00000634876.2	n.2593+8838A>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0103 AC: 1562 AN: 152224 Hom.: 18 Cov.: 33

Gnomad AFR AF: 0.00294

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0133

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00931

Gnomad FIN AF: 0.00273

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0160

Gnomad OTH AF: 0.0196

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

GnomAD4 genome AF: 0.0102 AC: 1559 AN: 152342 Hom.: 18 Cov.: 33 AF XY: 0.00969 AC XY: 722 AN XY: 74494

Gnomad4 AFR AF: 0.00291

Gnomad4 AMR AF: 0.0133

Gnomad4 ASJ AF: 0.00461

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00932

Gnomad4 FIN AF: 0.00273

Gnomad4 NFE AF: 0.0160

Gnomad4 OTH AF: 0.0194

Alfa AF: 0.00617 Hom.: 0

Bravo AF: 0.0109

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.4
DANN	Benign	0.68

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: rs28364028; hg19: chr17-43894111;