7-128753896-G-A

Position:

• chr7-128753896-G-A

Variant summary

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

The NM_001219.5(CALU):​c.222-366G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.788 in 152,206 control chromosomes in the GnomAD database, including 48,027 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 0.79 (48027 hom., cov: 33)
• Consequence: CALU NM_001219.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.219

Genes affected

CALU (HGNC:1458): (calumenin) The product of this gene is a calcium-binding protein localized in the endoplasmic reticulum (ER) and it is involved in such ER functions as protein folding and sorting. This protein belongs to a family of multiple EF-hand proteins (CERC) that include reticulocalbin, ERC-55, and Cab45 and the product of this gene. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Oct 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.918 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CALU	NM_001219.5	c.222-366G>A		intron_variant		ENST00000249364.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CALU	ENST00000249364.9	c.222-366G>A		intron_variant		1	NM_001219.5

Frequencies

GnomAD3 genomes AF: 0.788 AC: 119837 AN: 152088 Hom.: 47964 Cov.: 33

Gnomad AFR AF: 0.925

Gnomad AMI AF: 0.739

Gnomad AMR AF: 0.787

Gnomad ASJ AF: 0.790

Gnomad EAS AF: 0.940

Gnomad SAS AF: 0.725

Gnomad FIN AF: 0.659

Gnomad MID AF: 0.693

Gnomad NFE AF: 0.719

Gnomad OTH AF: 0.777

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

GnomAD4 genome AF: 0.788 AC: 119954 AN: 152206 Hom.: 48027 Cov.: 33 AF XY: 0.785 AC XY: 58413 AN XY: 74402

Gnomad4 AFR AF: 0.926

Gnomad4 AMR AF: 0.787

Gnomad4 ASJ AF: 0.790

Gnomad4 EAS AF: 0.940

Gnomad4 SAS AF: 0.725

Gnomad4 FIN AF: 0.659

Gnomad4 NFE AF: 0.719

Gnomad4 OTH AF: 0.773

Alfa AF: 0.737 Hom.: 59102

Bravo AF: 0.812

Asia WGS AF: 0.819 AC: 2848 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.3
DANN	Benign	0.57

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: rs109829; hg19: chr7-128393950;