7-128756628-G-T

Variant names:

• chr7-128756628-G-T
• rs3778760
• NM_001219.5:c.415+2173G>T

Variant summary

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

The NM_001219.5(CALU):​c.415+2173G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 150,836 control chromosomes in the GnomAD database, including 6,879 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 0.28 (6879 hom., cov: 32)
• Consequence: CALU NM_001219.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0860
• Publications: 6 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.373 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CALU	NM_001219.5	c.415+2173G>T		intron_variant	Intron 3 of 6	ENST00000249364.9	NP_001210.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CALU	ENST00000249364.9	c.415+2173G>T		intron_variant	Intron 3 of 6	1	NM_001219.5	ENSP00000249364.4

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42357 AN: 150722 Hom.: 6875 Cov.: 32

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.523

Gnomad AMR AF: 0.252

Gnomad ASJ AF: 0.380

Gnomad EAS AF: 0.0723

Gnomad SAS AF: 0.236

Gnomad FIN AF: 0.289

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.377

Gnomad OTH AF: 0.311

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

GnomAD4 genome AF: 0.281 AC: 42359 AN: 150836 Hom.: 6879 Cov.: 32 AF XY: 0.276 AC XY: 20305 AN XY: 73606

African (AFR) AF: 0.145 AC: 5934 AN: 40894

American (AMR) AF: 0.251 AC: 3816 AN: 15192

Ashkenazi Jewish (ASJ) AF: 0.380 AC: 1312 AN: 3454

East Asian (EAS) AF: 0.0731 AC: 370 AN: 5062

South Asian (SAS) AF: 0.238 AC: 1137 AN: 4784

European-Finnish (FIN) AF: 0.289 AC: 3034 AN: 10502

Middle Eastern (MID) AF: 0.395 AC: 109 AN: 276

European-Non Finnish (NFE) AF: 0.377 AC: 25534 AN: 67688

Other (OTH) AF: 0.307 AC: 638 AN: 2076

Alfa AF: 0.341 Hom.: 5155

Bravo AF: 0.274

Asia WGS AF: 0.142 AC: 494 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	7.7
DANN	Benign	0.83
PhyloP100		-0.086
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: rs3778760; hg19: chr7-128396682;