21-26564526-G-C

Variant names:

• chr21-26564526-G-C
• rs222969
• NM_001320768.2:c.176+1740C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001320768.2(CYYR1):​c.176+1740C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
• Consequence: CYYR1 NM_001320768.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.27
• Publications: 1 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.0
DANN	Benign	0.43
PhyloP100		1.3

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: rs222969; hg19: chr21-27936845;