rs12938476

Variant names:

• chr17-45735531-T-C
• rs12938476
• ENST00000634540.1:c.-492-71479T>C

Variant summary

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

The NM_001303016.1(LINC02210-CRHR1):​c.-185+62629T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.399 in 151,984 control chromosomes in the GnomAD database, including 12,289 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 0.40 (12289 hom., cov: 31)
• Consequence: LINC02210-CRHR1 NM_001303016.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.129
• Publications: 20 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]

ENSG00000265547 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.503 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001303016.1. 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+62629T>C		intron	N/A	NP_001289945.1	B4DMR5
	LINC02210-CRHR1	NM_001256299.3		c.-492-71479T>C		intron	N/A	NP_001243228.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LINC02210-CRHR1	ENST00000634540.1	TSL:2	c.-492-71479T>C		intron	N/A	ENSP00000488912.1
	LINC02210-CRHR1	ENST00000587305.1	TSL:5	n.447+62629T>C		intron	N/A
	ENSG00000265547	ENST00000717263.1		n.246+322A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.399 AC: 60557 AN: 151866 Hom.: 12272 Cov.: 31

Gnomad AFR AF: 0.375

Gnomad AMI AF: 0.335

Gnomad AMR AF: 0.408

Gnomad ASJ AF: 0.471

Gnomad EAS AF: 0.497

Gnomad SAS AF: 0.520

Gnomad FIN AF: 0.262

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.412

Gnomad OTH AF: 0.456

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

GnomAD4 genome AF: 0.399 AC: 60607 AN: 151984 Hom.: 12289 Cov.: 31 AF XY: 0.394 AC XY: 29292 AN XY: 74288

African (AFR) AF: 0.375 AC: 15539 AN: 41430

American (AMR) AF: 0.408 AC: 6229 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.471 AC: 1634 AN: 3470

East Asian (EAS) AF: 0.498 AC: 2566 AN: 5152

South Asian (SAS) AF: 0.520 AC: 2502 AN: 4816

European-Finnish (FIN) AF: 0.262 AC: 2772 AN: 10596

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.412 AC: 27963 AN: 67946

Other (OTH) AF: 0.453 AC: 958 AN: 2114

Alfa AF: 0.415 Hom.: 22799

Bravo AF: 0.407

Asia WGS AF: 0.460 AC: 1601 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.5
DANN	Benign	0.82
PhyloP100		-0.13
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: rs12938476; hg19: chr17-43812897;