5-79700227-A-G

Variant names:

• chr5-79700227-A-G
• rs6870619
• NM_153610.5:c.149+10171A>G

Variant summary

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

The NM_153610.5(CMYA5):​c.149+10171A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.365 in 152,150 control chromosomes in the GnomAD database, including 11,264 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 0.37 (11264 hom., cov: 33)
• Consequence: CMYA5 NM_153610.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.433
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.507 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CMYA5	NM_153610.5	c.149+10171A>G		intron_variant	Intron 1 of 12	ENST00000446378.3	NP_705838.3
CMYA5	XM_047416911.1	c.149+10171A>G		intron_variant	Intron 1 of 5		XP_047272867.1
CMYA5	XR_001742036.3	n.221+10171A>G		intron_variant	Intron 1 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CMYA5	ENST00000446378.3	c.149+10171A>G		intron_variant	Intron 1 of 12	5	NM_153610.5	ENSP00000394770.2

Frequencies

GnomAD3 genomes AF: 0.365 AC: 55501 AN: 152032 Hom.: 11247 Cov.: 33

Gnomad AFR AF: 0.513

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.490

Gnomad ASJ AF: 0.254

Gnomad EAS AF: 0.473

Gnomad SAS AF: 0.252

Gnomad FIN AF: 0.306

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.266

Gnomad OTH AF: 0.331

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

GnomAD4 genome AF: 0.365 AC: 55557 AN: 152150 Hom.: 11264 Cov.: 33 AF XY: 0.369 AC XY: 27446 AN XY: 74370

African (AFR) AF: 0.513 AC: 21286 AN: 41480

American (AMR) AF: 0.490 AC: 7491 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.254 AC: 881 AN: 3468

East Asian (EAS) AF: 0.473 AC: 2448 AN: 5180

South Asian (SAS) AF: 0.252 AC: 1213 AN: 4820

European-Finnish (FIN) AF: 0.306 AC: 3243 AN: 10594

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.266 AC: 18083 AN: 68008

Other (OTH) AF: 0.329 AC: 694 AN: 2108

Alfa AF: 0.309 Hom.: 21633

Bravo AF: 0.388

Asia WGS AF: 0.359 AC: 1247 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	1.2
DANN	Benign	0.88
PhyloP100		-0.43
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: rs6870619; hg19: chr5-78996050;