rs222969

Positions:

• chr21-26564526-G-A
• chr21-26564526-G-C
• chr21-26564526-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.27

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

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
CYYR1	NM_001320768.2	c.176+1740C>T		intron_variant		ENST00000652641.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYYR1	ENST00000652641.2	c.176+1740C>T		intron_variant			NM_001320768.2	A2
CYYR1	ENST00000299340.9	c.176+1740C>T		intron_variant		1		P2
CYYR1	ENST00000400043.3	c.176+1740C>T		intron_variant		1
CYYR1-AS1	ENST00000357401.3	n.2117-3431G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.801 AC: 121747 AN: 152028 Hom.: 48870 Cov.: 33

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

Gnomad4 AFR exome AF: 0.871

Gnomad4 AMR exome AF: 0.793

Gnomad4 ASJ exome AF: 0.713

Gnomad4 EAS exome AF: 0.869

Gnomad4 SAS exome AF: 0.841

Gnomad4 FIN exome AF: 0.769

Gnomad4 NFE exome AF: 0.787

Gnomad4 OTH exome AF: 0.790

GnomAD4 genome AF: 0.801 AC: 121848 AN: 152146 Hom.: 48914 Cov.: 33 AF XY: 0.801 AC XY: 59605 AN XY: 74378

Gnomad4 AFR AF: 0.860

Gnomad4 AMR AF: 0.787

Gnomad4 ASJ AF: 0.713

Gnomad4 EAS AF: 0.866

Gnomad4 SAS AF: 0.849

Gnomad4 FIN AF: 0.744

Gnomad4 NFE AF: 0.774

Gnomad4 OTH AF: 0.763

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
DANN	Benign	0.49

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

LitVar

Other links and lift over

dbSNP: rs222969; hg19: chr21-27936845;