rs241031

Variant names:

• chr17-45656938-T-C
• rs241031
• ENST00000634540.1:c.-493+26780T>C

Variant summary

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

The ENST00000634540.1(LINC02210-CRHR1):​c.-493+26780T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 152,240 control chromosomes in the GnomAD database, including 2,146 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 0.14 (2146 hom., cov: 32)
• Consequence: LINC02210-CRHR1 ENST00000634540.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.652
• Publications: 26 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]

ENSG00000306349 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LINC02210-CRHR1	NM_001303016.1	c.-260-15889T>C		intron_variant	Intron 2 of 12		NP_001289945.1
LINC02210-CRHR1	NM_001256299.3	c.-493+26780T>C		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.-493+26780T>C		intron_variant	Intron 3 of 14	2		ENSP00000488912.1
LINC02210-CRHR1	ENST00000587305.1	n.372-15889T>C		intron_variant	Intron 2 of 4	5
ENSG00000306349	ENST00000817145.1	n.293+748A>G		intron_variant	Intron 3 of 4

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21858 AN: 152122 Hom.: 2148 Cov.: 32

Gnomad AFR AF: 0.0431

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.240

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0742

Gnomad FIN AF: 0.0650

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.186

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

GnomAD4 genome AF: 0.144 AC: 21848 AN: 152240 Hom.: 2146 Cov.: 32 AF XY: 0.134 AC XY: 10000 AN XY: 74446

African (AFR) AF: 0.0430 AC: 1785 AN: 41552

American (AMR) AF: 0.176 AC: 2691 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.240 AC: 834 AN: 3472

East Asian (EAS) AF: 0.00154 AC: 8 AN: 5188

South Asian (SAS) AF: 0.0742 AC: 358 AN: 4822

European-Finnish (FIN) AF: 0.0650 AC: 690 AN: 10614

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.217 AC: 14744 AN: 67992

Other (OTH) AF: 0.183 AC: 387 AN: 2116

Alfa AF: 0.196 Hom.: 1911

Bravo AF: 0.149

Asia WGS AF: 0.0310 AC: 110 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.81
DANN	Benign	0.25
PhyloP100		-0.65
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: rs241031; hg19: chr17-43734304;