rs1880756

Variant names:

• chr17-45749300-C-T
• rs1880756
• ENST00000634540.1:c.-492-57710C>T

Variant summary

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

The ENST00000634540.1(LINC02210-CRHR1):​c.-492-57710C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 152,180 control chromosomes in the GnomAD database, including 7,112 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 0.28 (7112 hom., cov: 33)
• Consequence: LINC02210-CRHR1 ENST00000634540.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.407
• Publications: 13 publications found

Genes affected

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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.337 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LINC02210-CRHR1	NM_001303016.1	c.-184-57710C>T		intron_variant	Intron 3 of 12		NP_001289945.1
LINC02210-CRHR1	NM_001256299.3	c.-492-57710C>T		intron_variant	Intron 3 of 14		NP_001243228.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LINC02210-CRHR1	ENST00000634540.1	c.-492-57710C>T		intron_variant	Intron 3 of 14	2		ENSP00000488912.1
LINC02210-CRHR1	ENST00000587305.1	n.448-57710C>T		intron_variant	Intron 3 of 4	5

Frequencies

GnomAD3 genomes AF: 0.285 AC: 43277 AN: 152062 Hom.: 7105 Cov.: 33

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.527

Gnomad AMR AF: 0.337

Gnomad ASJ AF: 0.286

Gnomad EAS AF: 0.261

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.470

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.341

Gnomad OTH AF: 0.270

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

GnomAD4 genome AF: 0.285 AC: 43297 AN: 152180 Hom.: 7112 Cov.: 33 AF XY: 0.292 AC XY: 21733 AN XY: 74404

African (AFR) AF: 0.122 AC: 5078 AN: 41520

American (AMR) AF: 0.337 AC: 5153 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.286 AC: 993 AN: 3468

East Asian (EAS) AF: 0.261 AC: 1348 AN: 5170

South Asian (SAS) AF: 0.297 AC: 1433 AN: 4818

European-Finnish (FIN) AF: 0.470 AC: 4965 AN: 10574

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.341 AC: 23198 AN: 68008

Other (OTH) AF: 0.270 AC: 571 AN: 2112

Alfa AF: 0.296 Hom.: 6130

Bravo AF: 0.267

Asia WGS AF: 0.287 AC: 997 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.0
DANN	Benign	0.69
PhyloP100		-0.41
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: rs1880756; hg19: chr17-43826666;