7-72183011-A-G

Variant names:

• chr7-72183011-A-G
• rs4577845
• NM_031468.4:c.245-76717T>C

Variant summary

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

The NM_031468.4(CALN1):​c.245-76717T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.507 in 151,842 control chromosomes in the GnomAD database, including 21,738 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 0.51 (21738 hom., cov: 30)
• Consequence: CALN1 NM_031468.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.547
• Publications: 4 publications found

Genes affected

CALN1 (HGNC:13248): (calneuron 1) This gene encodes a protein with high similarity to the calcium-binding proteins of the calmodulin family. The encoded protein contains two EF-hand domains and potential calcium-binding sites. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.653 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CALN1	NM_031468.4	c.245-76717T>C		intron_variant	Intron 3 of 6	ENST00000395275.7	NP_113656.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CALN1	ENST00000395275.7	c.245-76717T>C		intron_variant	Intron 3 of 6	5	NM_031468.4	ENSP00000378690.2

Frequencies

GnomAD3 genomes AF: 0.507 AC: 76957 AN: 151724 Hom.: 21730 Cov.: 30

Gnomad AFR AF: 0.332

Gnomad AMI AF: 0.630

Gnomad AMR AF: 0.447

Gnomad ASJ AF: 0.701

Gnomad EAS AF: 0.0368

Gnomad SAS AF: 0.358

Gnomad FIN AF: 0.523

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.658

Gnomad OTH AF: 0.531

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

GnomAD4 genome AF: 0.507 AC: 76990 AN: 151842 Hom.: 21738 Cov.: 30 AF XY: 0.495 AC XY: 36757 AN XY: 74190

African (AFR) AF: 0.332 AC: 13758 AN: 41412

American (AMR) AF: 0.447 AC: 6813 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.701 AC: 2430 AN: 3468

East Asian (EAS) AF: 0.0367 AC: 190 AN: 5178

South Asian (SAS) AF: 0.360 AC: 1730 AN: 4806

European-Finnish (FIN) AF: 0.523 AC: 5509 AN: 10524

Middle Eastern (MID) AF: 0.634 AC: 185 AN: 292

European-Non Finnish (NFE) AF: 0.658 AC: 44697 AN: 67898

Other (OTH) AF: 0.525 AC: 1105 AN: 2106

Alfa AF: 0.543 Hom.: 18152

Bravo AF: 0.495

Asia WGS AF: 0.184 AC: 645 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.8
DANN	Benign	0.59
PhyloP100		0.55
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: rs4577845; hg19: chr7-71647996;