Genetic Variant ENST00000634540.1:c.-492-74208G>A (chr17-45732802-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000634540.1(LINC02210-CRHR1):c.-492-74208G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 152,090 control chromosomes in the GnomAD database, including 4,305 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 0.21 ( 4303 hom., cov: 31)

Exomes 𝑓: 0.31 ( 2 hom. )

Consequence

LINC02210-CRHR1
ENST00000634540.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.336

Publications

8 publications found

Variant links:

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-CRHR1 links:

ENSG00000265547 (HGNC:):

ENSG00000265547 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.275 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LINC02210-CRHR1	NM_001303016.1		c.-185+59900G>A		intron	N/A	NP_001289945.1	B4DMR5
	LINC02210-CRHR1	NM_001256299.3		c.-492-74208G>A		intron	N/A	NP_001243228.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
LINC02210-CRHR1	ENST00000634540.1	TSL:2	c.-492-74208G>A	intron	N/A	ENSP00000488912.1
ENSG00000265547	ENST00000578936.1	TSL:4	n.176C>T	non_coding_transcript_exon	Exon 1 of 2
LINC02210-CRHR1	ENST00000587305.1	TSL:5	n.447+59900G>A	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.211

AC:

32089

AN:

151940

Hom.:

4300

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0488

Gnomad AMI

AF:

0.457

Gnomad AMR

AF:

0.273

Gnomad ASJ

AF:

0.172

Gnomad EAS

AF:

0.261

Gnomad SAS

AF:

0.287

Gnomad FIN

AF:

0.391

Gnomad MID

AF:

0.166

Gnomad NFE

AF:

0.259

Gnomad OTH

AF:

0.188

GnomAD4 exome

AF:

0.313

AC:

AN:

Hom.:

Cov.:

AF XY:

0.318

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.227

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.583

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.211

AC:

32089

AN:

152058

Hom.:

4303

Cov.:

AF XY:

0.219

AC XY:

16300

AN XY:

74314

show subpopulations

African (AFR)

AF:

0.0486

AC:

2019

AN:

41502

American (AMR)

AF:

0.273

AC:

4167

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.172

AC:

597

AN:

3470

East Asian (EAS)

AF:

0.260

AC:

1345

AN:

5168

South Asian (SAS)

AF:

0.288

AC:

1386

AN:

4818

European-Finnish (FIN)

AF:

0.391

AC:

4126

AN:

10546

Middle Eastern (MID)

AF:

0.161

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.259

AC:

17586

AN:

67964

Other (OTH)

AF:

0.189

AC:

400

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1210

2420

3629

4839

6049

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

340

680

1020

1360

1700

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.239

Hom.:

3039

Bravo

AF:

0.193

Asia WGS

AF:

0.273

AC:

949

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

(source)

DANN

Benign

0.57

PhyloP100

0.34

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over