7-71810328-G-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_031468.4(CALN1):c.658+8C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000264 in 1,613,010 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0013 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00016 (1 hom.)
• Consequence: CALN1 NM_031468.4 splice_region, intron
• Scores: Splicing: ADA: 0.00005913
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.837

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

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 7-71810328-G-T is Benign according to our data. Variant chr7-71810328-G-T is described in ClinVar as [Benign]. Clinvar id is 774654.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 191 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CALN1	NM_031468.4	c.658+8C>A		splice_region_variant, intron_variant		ENST00000395275.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CALN1	ENST00000395275.7	c.658+8C>A		splice_region_variant, intron_variant		5	NM_031468.4
CALN1	ENST00000329008.9	c.532+8C>A		splice_region_variant, intron_variant		1		P1
CALN1	ENST00000395276.6	c.532+8C>A		splice_region_variant, intron_variant		1		P1
CALN1	ENST00000431984.5	c.532+8C>A		splice_region_variant, intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.00126 AC: 191 AN: 152114 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00449

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000956

GnomAD3 exomes AF: 0.000411 AC: 103 AN: 250522 Hom.: 0 AF XY: 0.000266 AC XY: 36 AN XY: 135382

Gnomad AFR exome AF: 0.00566

Gnomad AMR exome AF: 0.000203

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000265

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000161 AC: 235 AN: 1460778 Hom.: 1 Cov.: 31 AF XY: 0.000129 AC XY: 94 AN XY: 726620

Gnomad4 AFR exome AF: 0.00478

Gnomad4 AMR exome AF: 0.000246

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000441

Gnomad4 OTH exome AF: 0.000215

GnomAD4 genome AF: 0.00125 AC: 191 AN: 152232 Hom.: 1 Cov.: 32 AF XY: 0.00125 AC XY: 93 AN XY: 74436

Gnomad4 AFR AF: 0.00448

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.000946

Alfa AF: 0.000554 Hom.: 0

Bravo AF: 0.00144

Asia WGS AF: 0.00144 AC: 6 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000594

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Aug 15, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	5.8
Dann	Benign	0.67

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000059
dbscSNV1_RF	Benign	0.0
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: rs73360079; hg19: chr7-71275313; COSMIC: COSV61147670;