10-12553330-A-G

Position:

• chr10-12553330-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001351032.2(CAMK1D):​c.-94A>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0123 in 1,613,980 control chromosomes in the GnomAD database, including 149 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0080 (4 hom., cov: 33)
  • Exomes 𝑓: 0.013 (145 hom.)
• Consequence: CAMK1D NM_001351032.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.766

Genes affected

CAMK1D (HGNC:19341): (calcium/calmodulin dependent protein kinase ID) This gene is a member of the calcium/calmodulin-dependent protein kinase 1 family, a subfamily of the serine/threonine kinases. The encoded protein is a component of the calcium-regulated calmodulin-dependent protein kinase cascade. It has been associated with multiple processes including regulation of granulocyte function, activation of CREB-dependent gene transcription, aldosterone synthesis, differentiation and activation of neutrophil cells, and apoptosis of erythroleukemia cells. Alternatively spliced transcript variants encoding different isoforms of this gene have been described. [provided by RefSeq, Jan 2015]

CAMK1D (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.010442436).
• BP6: Variant 10-12553330-A-G is Benign according to our data. Variant chr10-12553330-A-G is described in ClinVar as [Benign]. Clinvar id is 789893.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.0127 (18554/1461648) while in subpopulation NFE AF= 0.0156 (17319/1111818). AF 95% confidence interval is 0.0154. There are 145 homozygotes in gnomad4_exome. There are 8958 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1225 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAMK1D	NM_153498.4	c.198A>G	p.Ile66Met	missense_variant	2/11	ENST00000619168.5	NP_705718.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAMK1D	ENST00000619168.5	c.198A>G	p.Ile66Met	missense_variant	2/11	1	NM_153498.4	ENSP00000478874.1
CAMK1D	ENST00000378845.5	c.198A>G	p.Ile66Met	missense_variant	2/10	1		ENSP00000368122.1
CAMK1D	ENST00000487696.1	n.260-113406A>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.00804 AC: 1224 AN: 152214 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.00304

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00504

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00331

Gnomad FIN AF: 0.00188

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0144

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.00744 AC: 1870 AN: 251460 Hom.: 14 AF XY: 0.00779 AC XY: 1059 AN XY: 135906

Gnomad AFR exome AF: 0.00289

Gnomad AMR exome AF: 0.00350

Gnomad ASJ exome AF: 0.000893

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00271

Gnomad FIN exome AF: 0.00203

Gnomad NFE exome AF: 0.0133

Gnomad OTH exome AF: 0.00863

GnomAD4 exome AF: 0.0127 AC: 18554 AN: 1461648 Hom.: 145 Cov.: 32 AF XY: 0.0123 AC XY: 8958 AN XY: 727122

Gnomad4 AFR exome AF: 0.00278

Gnomad4 AMR exome AF: 0.00313

Gnomad4 ASJ exome AF: 0.000497

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00289

Gnomad4 FIN exome AF: 0.00197

Gnomad4 NFE exome AF: 0.0156

Gnomad4 OTH exome AF: 0.0103

GnomAD4 genome AF: 0.00804 AC: 1225 AN: 152332 Hom.: 4 Cov.: 33 AF XY: 0.00740 AC XY: 551 AN XY: 74500

Gnomad4 AFR AF: 0.00303

Gnomad4 AMR AF: 0.00503

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00331

Gnomad4 FIN AF: 0.00188

Gnomad4 NFE AF: 0.0144

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.0127 Hom.: 24

Bravo AF: 0.00785

TwinsUK AF: 0.0143 AC: 53

ALSPAC AF: 0.0161 AC: 62

ESP6500AA AF: 0.00250 AC: 11

ESP6500EA AF: 0.0119 AC: 102

ExAC AF: 0.00705 AC: 856

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.0135

EpiControl AF: 0.0149

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 07, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.45
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	13
DANN	Benign	0.96
DEOGEN2	Benign	0.052	T;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.81	T;T
MetaRNN	Benign	0.010	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.35	N;N
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-1.1	.;N
REVEL	Benign	0.11
Sift	Benign	0.12	.;T
Sift4G	Uncertain	0.043	D;D
Polyphen		0.086	B;.
Vest4		0.76
MVP		0.50
ClinPred		0.010	T
GERP RS		-9.9
Varity_R		0.15
gMVP		0.76

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: rs34194224; hg19: chr10-12595329; COSMIC: COSV66607178;