rs222949

Variant names:

• chr21-26539676-T-C
• rs222949
• NM_001320768.2:c.176+26590A>G

Variant summary

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

The NM_001320768.2(CYYR1):​c.176+26590A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0149 in 152,336 control chromosomes in the GnomAD database, including 34 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 0.015 (34 hom., cov: 32)
• Consequence: CYYR1 NM_001320768.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.595

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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0811 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYYR1	NM_001320768.2	c.176+26590A>G		intron_variant	Intron 2 of 3	ENST00000652641.2	NP_001307697.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYYR1	ENST00000652641.2	c.176+26590A>G		intron_variant	Intron 2 of 3		NM_001320768.2	ENSP00000498505.1
CYYR1	ENST00000299340.9	c.176+26590A>G		intron_variant	Intron 2 of 3	1		ENSP00000299340.4
CYYR1	ENST00000400043.3	c.176+26590A>G		intron_variant	Intron 2 of 3	1		ENSP00000382918.3
CYYR1-AS1	ENST00000357401.3	n.308-10643T>C		intron_variant	Intron 2 of 3	2

Frequencies

GnomAD3 genomes AF: 0.0148 AC: 2258 AN: 152218 Hom.: 33 Cov.: 32

Gnomad AFR AF: 0.00965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0186

Gnomad ASJ AF: 0.0331

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0877

Gnomad FIN AF: 0.0135

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0123

Gnomad OTH AF: 0.0201

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

GnomAD4 genome AF: 0.0149 AC: 2272 AN: 152336 Hom.: 34 Cov.: 32 AF XY: 0.0167 AC XY: 1244 AN XY: 74494

Gnomad4 AFR AF: 0.00991

Gnomad4 AMR AF: 0.0185

Gnomad4 ASJ AF: 0.0331

Gnomad4 EAS AF: 0.00154

Gnomad4 SAS AF: 0.0880

Gnomad4 FIN AF: 0.0135

Gnomad4 NFE AF: 0.0123

Gnomad4 OTH AF: 0.0203

Alfa AF: 0.0133 Hom.: 1

Bravo AF: 0.0133

Asia WGS AF: 0.0460 AC: 159 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.1
DANN	Benign	0.41

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: rs222949; hg19: chr21-27911995;