chr17-45649293-A-C

Variant names:

• chr17-45649293-A-C
• rs439945
• ENST00000634540.1:c.-493+19135A>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+19135A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.66 in 152,146 control chromosomes in the GnomAD database, including 35,921 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 0.66 (35914 hom., cov: 32)
  • Exomes 𝑓: 0.67 (7 hom.)
• Consequence: LINC02210-CRHR1 ENST00000634540.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0570
• Publications: 16 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]

LINC02210 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.869 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000634540.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LINC02210-CRHR1	NM_001303016.1		c.-261+19135A>C		intron	N/A	NP_001289945.1
	LINC02210-CRHR1	NM_001256299.3		c.-493+19135A>C		intron	N/A	NP_001243228.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LINC02210-CRHR1	ENST00000634540.1	TSL:2	c.-493+19135A>C		intron	N/A	ENSP00000488912.1
	LINC02210	ENST00000591271.5	TSL:3	n.3815A>C		non_coding_transcript_exon	Exon 4 of 4
	LINC02210-CRHR1	ENST00000587305.1	TSL:5	n.371+19135A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.660 AC: 100362 AN: 151996 Hom.: 35897 Cov.: 32

Gnomad AFR AF: 0.369

Gnomad AMI AF: 0.637

Gnomad AMR AF: 0.724

Gnomad ASJ AF: 0.725

Gnomad EAS AF: 0.891

Gnomad SAS AF: 0.890

Gnomad FIN AF: 0.905

Gnomad MID AF: 0.706

Gnomad NFE AF: 0.747

Gnomad OTH AF: 0.664

GnomAD4 exome AF: 0.667 AC: 20 AN: 30 Hom.: 7 Cov.: 0 AF XY: 0.600 AC XY: 12 AN XY: 20

African (AFR) AF: 0.500 AC: 1 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 1.00 AC: 2 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.636 AC: 14 AN: 22

Other (OTH) AF: 0.750 AC: 3 AN: 4

GnomAD4 genome AF: 0.660 AC: 100415 AN: 152116 Hom.: 35914 Cov.: 32 AF XY: 0.676 AC XY: 50256 AN XY: 74370

African (AFR) AF: 0.369 AC: 15314 AN: 41470

American (AMR) AF: 0.725 AC: 11073 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.725 AC: 2517 AN: 3472

East Asian (EAS) AF: 0.891 AC: 4604 AN: 5168

South Asian (SAS) AF: 0.891 AC: 4295 AN: 4822

European-Finnish (FIN) AF: 0.905 AC: 9599 AN: 10602

Middle Eastern (MID) AF: 0.711 AC: 209 AN: 294

European-Non Finnish (NFE) AF: 0.747 AC: 50816 AN: 67990

Other (OTH) AF: 0.669 AC: 1411 AN: 2110

Alfa AF: 0.725 Hom.: 32359

Bravo AF: 0.631

Asia WGS AF: 0.854 AC: 2969 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.1
DANN	Benign	0.43
PhyloP100		-0.057
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: rs439945; hg19: chr17-43726659;