dbSNP rs222969: CYYR1:c.176+1740C>T (chr21-26564526-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 NM_001320768.2(CYYR1):c.176+1740C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.795 in 320,148 control chromosomes in the GnomAD database, including 101,424 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 0.80 ( 48914 hom., cov: 33)

Exomes 𝑓: 0.79 ( 52510 hom. )

Consequence

CYYR1
NM_001320768.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.27

Publications

1 publications found

Variant links:

Genes affected

CYYR1 (HGNC:16274): (cysteine and tyrosine rich 1) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

CYYR1 links:

CYYR1-AS1 (HGNC:39560): (CYYR1 antisense RNA 1)

CYYR1-AS1 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 (EAS) allele frequency at 95% confidence interval = 0.853 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYYR1	NM_001320768.2 link	c.176+1740C>T		intron_variant	Intron 2 of 3	ENST00000652641.2	NP_001307697.2	Q96J86-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CYYR1	ENST00000652641.2 link	c.176+1740C>T	intron_variant	Intron 2 of 3		NM_001320768.2	ENSP00000498505.1	Q96J86-2
CYYR1	ENST00000299340.9 link	c.176+1740C>T	intron_variant	Intron 2 of 3	1		ENSP00000299340.4	Q96J86-1
CYYR1	ENST00000400043.3 link	c.176+1740C>T	intron_variant	Intron 2 of 3	1		ENSP00000382918.3	Q96J86-3
CYYR1-AS1	ENST00000357401.3 link	n.2117-3431G>A	intron_variant	Intron 3 of 3	2

Frequencies

GnomAD3 genomes

AF:

0.801

AC:

121747

AN:

152028

Hom.:

48870

Cov.:

show subpopulations

Gnomad AFR

AF:

0.860

Gnomad AMI

AF:

0.777

Gnomad AMR

AF:

0.787

Gnomad ASJ

AF:

0.713

Gnomad EAS

AF:

0.866

Gnomad SAS

AF:

0.850

Gnomad FIN

AF:

0.744

Gnomad MID

AF:

0.731

Gnomad NFE

AF:

0.774

Gnomad OTH

AF:

0.761

GnomAD4 exome

AF:

0.790

AC:

132668

AN:

168002

Hom.:

52510

AF XY:

0.789

AC XY:

63783

AN XY:

80870

show subpopulations

African (AFR)

AF:

0.871

AC:

2536

AN:

2912

American (AMR)

AF:

0.793

AC:

138

AN:

174

Ashkenazi Jewish (ASJ)

AF:

0.713

AC:

757

AN:

1062

East Asian (EAS)

AF:

0.869

AC:

608

AN:

700

South Asian (SAS)

AF:

0.841

AC:

2809

AN:

3340

European-Finnish (FIN)

AF:

0.769

AC:

AN:

Middle Eastern (MID)

AF:

0.747

AC:

245

AN:

328

European-Non Finnish (NFE)

AF:

0.787

AC:

121156

AN:

153888

Other (OTH)

AF:

0.790

AC:

4379

AN:

5546

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

1401

2802

4203

5604

7005

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3890

7780

11670

15560

19450

<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:

0.801

AC:

121848

AN:

152146

Hom.:

48914

Cov.:

AF XY:

0.801

AC XY:

59605

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.860

AC:

35701

AN:

41506

American (AMR)

AF:

0.787

AC:

12020

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.713

AC:

2477

AN:

3472

East Asian (EAS)

AF:

0.866

AC:

4497

AN:

5190

South Asian (SAS)

AF:

0.849

AC:

4094

AN:

4822

European-Finnish (FIN)

AF:

0.744

AC:

7865

AN:

10572

Middle Eastern (MID)

AF:

0.728

AC:

214

AN:

294

European-Non Finnish (NFE)

AF:

0.774

AC:

52657

AN:

67994

Other (OTH)

AF:

0.763

AC:

1614

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1259

2519

3778

5038

6297

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

874

1748

2622

3496

4370

<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:

0.783

Hom.:

9465

Bravo

AF:

0.803

Asia WGS

AF:

0.848

AC:

2949

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

3.4

(source)

DANN

Benign

0.49

PhyloP100

1.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over