rs77767215

Positions:

• chr5-79725700-C-T

Variant summary

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

The NM_153610.5(CMYA5):​c.150-3215C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0656 in 152,248 control chromosomes in the GnomAD database, including 489 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 0.066 (489 hom., cov: 33)
• Consequence: CMYA5 NM_153610.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.73

Genes affected

CMYA5 (HGNC:14305): (cardiomyopathy associated 5) Predicted to enable identical protein binding activity. Predicted to act upstream of or within negative regulation of calcineurin-NFAT signaling cascade; negative regulation of phosphoprotein phosphatase activity; and regulation of skeletal muscle adaptation. Located in cytosol; nuclear speck; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.236 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CMYA5	NM_153610.5	c.150-3215C>T		intron_variant		ENST00000446378.3	NP_705838.3
CMYA5	XM_047416911.1	c.150-3215C>T		intron_variant			XP_047272867.1
CMYA5	XR_001742036.3	n.222-3215C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CMYA5	ENST00000446378.3	c.150-3215C>T		intron_variant		5	NM_153610.5	ENSP00000394770	P1

Frequencies

GnomAD3 genomes AF: 0.0655 AC: 9968 AN: 152130 Hom.: 488 Cov.: 33

Gnomad AFR AF: 0.0663

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.0315

Gnomad ASJ AF: 0.0320

Gnomad EAS AF: 0.248

Gnomad SAS AF: 0.0215

Gnomad FIN AF: 0.0907

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0612

Gnomad OTH AF: 0.0483

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

GnomAD4 genome AF: 0.0656 AC: 9980 AN: 152248 Hom.: 489 Cov.: 33 AF XY: 0.0671 AC XY: 4995 AN XY: 74432

Gnomad4 AFR AF: 0.0665

Gnomad4 AMR AF: 0.0314

Gnomad4 ASJ AF: 0.0320

Gnomad4 EAS AF: 0.248

Gnomad4 SAS AF: 0.0218

Gnomad4 FIN AF: 0.0907

Gnomad4 NFE AF: 0.0612

Gnomad4 OTH AF: 0.0478

Alfa AF: 0.0603 Hom.: 35

Bravo AF: 0.0640

Asia WGS AF: 0.118 AC: 412 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.85
DANN	Benign	0.81

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: rs77767215; hg19: chr5-79021523;