rs1555514404

Variant names:

• chr16-28878665-G-A
• rs1555514404
• NM_004320.6:c.-7G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Moderate BP6_Moderate

The NM_004320.6(ATP2A1):​c.-7G>A variant causes a 5 prime UTR change. The variant allele was found at a frequency of 0.00000486 in 1,439,868 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000049 (0 hom.)
• Consequence: ATP2A1 NM_004320.6 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.94
• Publications: 0 publications found

Genes affected

ATP2A1 (HGNC:811): (ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 1) This gene encodes one of the SERCA Ca(2+)-ATPases, which are intracellular pumps located in the sarcoplasmic or endoplasmic reticula of muscle cells. This enzyme catalyzes the hydrolysis of ATP coupled with the translocation of calcium from the cytosol to the sarcoplasmic reticulum lumen, and is involved in muscular excitation and contraction. Mutations in this gene cause some autosomal recessive forms of Brody disease, characterized by increasing impairment of muscular relaxation during exercise. Alternative splicing results in three transcript variants encoding different isoforms. [provided by RefSeq, Oct 2013]

ATP2A1-AS1 (HGNC:51370): (ATP2A1 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• BP6: Variant 16-28878665-G-A is Benign according to our data. Variant chr16-28878665-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 514365.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004320.6. 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
	ATP2A1	NM_004320.6	MANE Select	c.-7G>A		5_prime_UTR	Exon 1 of 23	NP_004311.1	O14983-2
	ATP2A1	NM_173201.5		c.-7G>A		5_prime_UTR	Exon 1 of 22	NP_775293.1	O14983-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP2A1	ENST00000395503.9	TSL:1 MANE Select	c.-7G>A		5_prime_UTR	Exon 1 of 23	ENSP00000378879.5	O14983-2
	ATP2A1	ENST00000971328.1		c.-7G>A		5_prime_UTR	Exon 1 of 23	ENSP00000641387.1
	ATP2A1	ENST00000357084.7	TSL:2	c.-7G>A		5_prime_UTR	Exon 1 of 22	ENSP00000349595.3	O14983-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000486 AC: 7 AN: 1439868 Hom.: 0 Cov.: 31 AF XY: 0.00000560 AC XY: 4 AN XY: 714270

African (AFR) AF: 0.00 AC: 0 AN: 33128

American (AMR) AF: 0.00 AC: 0 AN: 41244

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25630

East Asian (EAS) AF: 0.000154 AC: 6 AN: 38988

South Asian (SAS) AF: 0.00 AC: 0 AN: 83638

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51676

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5748

European-Non Finnish (NFE) AF: 9.09e-7 AC: 1 AN: 1100274

Other (OTH) AF: 0.00 AC: 0 AN: 59542

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	20
DANN	Benign	0.93
PhyloP100		3.9
PromoterAI		0.13	Neutral

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: rs1555514404; hg19: chr16-28889986;