rs222973

Variant names:

• chr21-26506750-T-A
• rs222973
• NM_001320768.2:c.177-26321A>T

Your query was ambiguous. Multiple possible variants found:

• chr21-26506750-T-A
• chr21-26506750-T-C

Variant summary

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

The NM_001320768.2(CYYR1):​c.177-26321A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.754 in 151,726 control chromosomes in the GnomAD database, including 43,871 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 0.75 (43868 hom., cov: 28)
  • Exomes 𝑓: 0.67 (3 hom.)
• Consequence: CYYR1 NM_001320768.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0890
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.873 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001320768.2. 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
	CYYR1	NM_001320768.2	MANE Select	c.177-26321A>T		intron	N/A	NP_001307697.2	Q96J86-2
	CYYR1	NM_052954.5		c.177-26321A>T		intron	N/A	NP_443186.3	Q96J86-1
	CYYR1	NR_135472.2		n.690-26321A>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYYR1	ENST00000652641.2	MANE Select	c.177-26321A>T		intron	N/A	ENSP00000498505.1	Q96J86-2
	CYYR1	ENST00000299340.9	TSL:1	c.177-26321A>T		intron	N/A	ENSP00000299340.4	Q96J86-1
	CYYR1	ENST00000400043.3	TSL:1	c.177-26321A>T		intron	N/A	ENSP00000382918.3	Q96J86-3

Frequencies

GnomAD3 genomes AF: 0.754 AC: 114329 AN: 151596 Hom.: 43811 Cov.: 28

Gnomad AFR AF: 0.880

Gnomad AMI AF: 0.820

Gnomad AMR AF: 0.758

Gnomad ASJ AF: 0.705

Gnomad EAS AF: 0.468

Gnomad SAS AF: 0.648

Gnomad FIN AF: 0.689

Gnomad MID AF: 0.744

Gnomad NFE AF: 0.718

Gnomad OTH AF: 0.732

GnomAD4 exome AF: 0.667 AC: 8 AN: 12 Hom.: 3 Cov.: 0 AF XY: 0.500 AC XY: 4 AN XY: 8

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.700 AC: 7 AN: 10

Other (OTH) AF: 0.500 AC: 1 AN: 2

GnomAD4 genome AF: 0.754 AC: 114442 AN: 151714 Hom.: 43868 Cov.: 28 AF XY: 0.751 AC XY: 55622 AN XY: 74112

African (AFR) AF: 0.880 AC: 36438 AN: 41396

American (AMR) AF: 0.758 AC: 11543 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.705 AC: 2449 AN: 3472

East Asian (EAS) AF: 0.468 AC: 2397 AN: 5124

South Asian (SAS) AF: 0.647 AC: 3079 AN: 4762

European-Finnish (FIN) AF: 0.689 AC: 7265 AN: 10544

Middle Eastern (MID) AF: 0.745 AC: 219 AN: 294

European-Non Finnish (NFE) AF: 0.718 AC: 48760 AN: 67882

Other (OTH) AF: 0.734 AC: 1547 AN: 2108

Alfa AF: 0.728 Hom.: 4765

Bravo AF: 0.766

Asia WGS AF: 0.602 AC: 2098 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.5
DANN	Benign	0.72
PhyloP100		0.089
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: rs222973; hg19: chr21-27879069;