rs376321664

Variant names:

• chr19-16520420-C-A
• rs376321664
• NM_006387.6:c.2289G>T

Your query was ambiguous. Multiple possible variants found:

• chr19-16520420-C-A
• chr19-16520420-C-G
• chr19-16520420-C-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Moderate BS2

The NM_006387.6(CHERP):​c.2289G>T​(p.Ser763Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,858 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S763S) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: CHERP NM_006387.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.808
• Publications: 0 publications found

Genes affected

CHERP (HGNC:16930): (calcium homeostasis endoplasmic reticulum protein) Enables transmembrane transporter binding activity. Involved in positive regulation of calcineurin-NFAT signaling cascade and release of sequestered calcium ion into cytosol. Acts upstream of or within cellular calcium ion homeostasis and negative regulation of cell population proliferation. Located in perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

C19orf44 (HGNC:26141): (chromosome 19 open reading frame 44)

C19orf44 Gene-Disease associations (from GenCC):

• inherited retinal dystrophy

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000141979 (HGNC:):

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BS2: High AC in GnomAdExome4 at 5 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006387.6. 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
	CHERP	NM_006387.6	MANE Select	c.2289G>T	p.Ser763Ser	synonymous	Exon 14 of 17	NP_006378.3
	C19orf44	NM_032207.4	MANE Select	c.*367C>A		3_prime_UTR	Exon 9 of 9	NP_115583.1	Q9H6X5-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHERP	ENST00000546361.7	TSL:1 MANE Select	c.2289G>T	p.Ser763Ser	synonymous	Exon 14 of 17	ENSP00000439856.2	Q8IWX8
	C19orf44	ENST00000221671.8	TSL:2 MANE Select	c.*367C>A		3_prime_UTR	Exon 9 of 9	ENSP00000221671.2	Q9H6X5-1
	C19orf44	ENST00000593380.1	TSL:1	n.*431C>A		non_coding_transcript_exon	Exon 9 of 9	ENSP00000472255.1	Q9H6X5-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461858 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 727238

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53394

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1112006

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	2.2
DANN	Benign	0.90
PhyloP100		-0.81

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs376321664; hg19: chr19-16631231;